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Volume 16, Number 18, Issue of September 15, 1996 pp. 5567-5582
Copyright ©1996 Society for NeuroscienceMultiple Channel Types Contribute to the Low-Voltage-Activated Calcium Current in Hippocampal CA3 Pyramidal Neurons
Robert B. Avery and Daniel Johnston Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
ABSTRACT
Hippocampal neurons exhibit low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium currents. We characterized the LVA current by recording whole-cell Ca2+ currents from acutely isolated rat hippocampal CA3 pyramidal neurons in 2 m Ca2+.
Long depolarizing steps to
50 mV revealed two components to the LVA current: transient and sustained. The transient phase had a fast decay time constant of 59 msec. The sustained phase persisted throughout the depolarization, even for steps lasting several seconds. The transient current was inhibited by the classic T-type channel antagonists Ni2+ and amiloride. The anticonvulsant phenytoin preferentially blocked the sustained phase, but ethosuximide had no effect. Steady-state inactivation of the transient component was half-maximal at
Nimodipine, an L-type channel antagonist, partly inhibited the sustained current. BayK-8644, an L-type channel agonist, potentiated the sustained current. Calciseptine, another L-type channel antagonist, inhibited the sustained component.
-Conotoxin-MVIIC, a nonselective toxin for HVA channels, had no effect on either of the LVA current components.
These results suggest that in physiologic Ca2+ more than one type of Ca2+ channel contributes to the LVA current in CA3 neurons. The transient current is carried by T-type channels. The sustained current is carried, at least in part, by dihydropyridine-sensitive channels. Thus, the designation ``low-voltage-activated'' should not be limited to T-type channels. These findings challenge the traditional designation of L-type channels as exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.
Key words: calcium channels; hippocampus; CA3; whole-cell patch; low-voltage-activated; T-type; L-type; nimodipine; ethosuximide; phenytoin
INTRODUCTION
Central neurons possess multiple types of voltage-gated calcium channels (Llinás and Yarom, 1981; Fisher et al., 1990
Single-channel recordings from guinea pigs suggest that T-type channels are particularly abundant on hippocampal CA3 pyramidal neurons, as compared with neurons from area CA1 or the dentate gyrus (Fisher et al., 1990
One reason that it has proved difficult to determine functional roles for LVA channels has been the lack of selective antagonists. Several drugs block T-type channels, but the quality of the blockade is quite variable across different cell types. In different cells, T-type channels also vary in their voltage dependence and kinetics. Therefore, to constrain and test hypotheses about how these channels contribute to specific cellular functions, it is necessary to characterize them in the neurons of interest.
We made whole-cell recordings from acutely isolated rat CA3 pyramidal neurons using physiological concentrations of Ca2+. We find that there are two distinct components to the LVA current. One current component is carried by T-type channels, and here we report the pharmacological profile and voltage dependence of the T-type current in CA3 cells. Further, we conclude that at least one other type of Ca2+ channel, which is sensitive to dihydropyridines, can be activated by a subthreshold stimulus near the resting potential. By definition, these channels should also be considered members of the LVA group.
MATERIALS AND METHODS
Cell preparation. Transverse hippocampal slices 500 µ thick were cut from rats 7-14 d old in ice-cold, oxygenated dissecting saline (see Solutions). Slices were incubated in a solution in which papain (10 U/ml, Worthington, Freehold, NJ), cysteine (5 m), EDTA (1 m), and mercaptoethanol (0.5 m) were added to 5 ml of the dissecting saline. The incubation occurred for 30 min at 37°C with oxygen flowing over the solution surface. Slices were rinsed with 1 mg/ml bovine serum albumin (BSA) and transferred to a room temperature holding chamber in which 1 m CaCl2 had been added to the dissecting saline. As needed, two slices were removed from the holding chamber and the CA3 region dissected out in 1 mg/ml BSA. Cells were isolated by gently triturating the tissue through a series of four or five fire-polished Pasteur pipettes. The diameter of the smallest pipette was ~250 µm. The resulting suspension was plated on a clean coverslip and allowed to settle for 5 min, at which time the dissecting saline was gradually replaced with the recording solution.Recordings. Patch pipettes were pulled from borosilicate glass (Drummond, Broomall, PA) on a two-stage vertical puller (Adams & List, Westbury, NY) and coated with SYLGARD. The resistance of the electrode in the bath was 2-5 M
. Cells were visualized by using an inverted microscope (Zeiss) equipped with Hoffman modulation optics. Target cells had pyramidal-shaped somata with few or no short processes. Cells were patch-clamped with an Axopatch 1-C (Axon Instruments, Foster City, CA). Most current records were analog-filtered at 2 kHz, digitized between 1 and 5 kHz, and digitally filtered off-line at 1 kHz. Tail currents, however, were filtered at 5 kHz and digitized at 20 kHz. Voltage commands were adjusted for tip potentials (
Nonlinear functions were fit to the data using DISCRETE (Provencher, 1976
Solutions. The dissecting saline included (in m): NaPIPES 110, NaCl 20, KCl 3, MgCl2 2, dextrose 10, and kynurenic acid 1, pH 7.4, 300 mOsm. The standard external recording saline included (in m): CaCl2 2, MgCl2 1.5, TEA-Cl 160, CsCl 5, 3,4 DAP 0.1, HEPES 10, and TTX 1 µ, pH 7.4, 300 mOsm. For most cells, the pipette solution included (in m): Tris base 28, Tris-PO4 70, TEA-Cl 40, MgCl2 5, BAPTA 5, and EGTA 5. The tip was filled with this solution; then the pipette was backfilled with the same solution plus an ATP-regenerating system composed of Tris-ATP 4, Tris-GTP 0.3, Tris-phosphocreatine 14, creatine phosphokinase 50 U/ml, and leupeptin 0.1, pH 7.3, 300 mOsm. A few recordings used the following pipette saline: TEA-MeSO3 115, MgCl2 5, BAPTA 5, EGTA 5, HEPES 20, plus the ATP-regenerating system, pH 7.3, 300 mOsm. We saw no difference in the currents between the two salines, although the recordings were more stable using the Tris-based saline.
Drugs. Nimodipine and D600 were purchased from Research Biochemicals (Natick, MA);
RESULTS
Whole-cell CA3 Ca2+ currents
This study had two major goals: to identify the types of Ca2+ channels that could be activated by subthreshold stimulation and to determine the usefulness (potency and selectivity) of blockers of these channels. Because we wanted to avoid shifts in the apparent voltage dependence attributable to high divalent concentrations and because we wanted to make our results directly transferrable to physiologic studies, we used Ca2+ at a physiologic concentration (2 m) as the charge carrier. Figure 1 shows Ca2+ currents evoked by 600 msec depolarizations from two different holding potentials. In Figure 1A currents were elicited from a holding potential of
Fig. 1. Ca2+ currents in CA3 pyramidal neurons. A, Currents elicited from a holding potential of) and
). Note the shoulder at negative potentials, indicating activation of LVA channels. On average, the maximum amplitude of current evoked from
[View Larger Version of this Image (21K GIF file)]
Long depolarizations to evoke LVA currents revealed two kinetically distinct components: one inactivating and one noninactivating (Fig. 1D, top trace). The inactivating phase of the current was best fit by the sum of two exponentials. The faster exponential had a time constant of 59 msec (n = 26). The slower time constant averaged 271 msec but was extremely variable. A reliable fit would probably require steps longer than 600 msec, although the small amplitude of this term would still make it difficult. The LVA current did not completely inactivate, and current persisted even for depolarizations lasting several seconds (Fig. 1D, bottom trace).
Switching the charge carrier from Ca2+ to equimolar Ba2+ reduced the peak of the LVA current but enhanced the sustained component. This meant a much smaller transient current. The HVA current was also larger in Ba2+ (compared with Ca2+, in 2 m Ba2+; LVA transient 66%, LVA sustained 113%, n = 4; HVA 120%, n = 6; data not shown). To control for less charge screening with Ba2+, we repeated the experiment with 3.5 m Ba2+. Although the currents were larger, the results were qualitiatively similar (n = 4). The differential response of the LVA components suggested that different channel types could underlie the two components. However, we could not exclude the possibility that the gating of a single channel type was altered in Ba2+.
We sought to determine if the two components result from the activation of the same or different types of Ca2+ channel. We differentiated between these two possibilities by comparing the pharmacological profile of the LVA current components.
Strategy for measuring current components
To test the selectivity of blockers of LVA channels, we established a protocol to measure drug effects on LVA and HVA channels within the same cell. We functionally defined LVA channels as those channels that could be activated by a subthreshold stimulus. Because the threshold for action-potential generation in hippocampal pyramidal cells is positive to
Fig. 2. Strategy for measuring components of the Ca2+ current. A, LVA currents were evoked by holding at
[View Larger Version of this Image (19K GIF file)]
The rationale for evoking HVA currents from a holding potential of
fast = 0.27 msec,
Because we ultimately wanted to use the HVA assay to test the specificity of LVA blockers, we also wanted to insure that our protocol to elicit HVA currents recruited all of the known types of HVA channels in CA3 neurons. We used common antagonists of HVA channels to test for the activation of pharmacologically defined HVA channels. HVA blockers were applied serially until the block by each agent reached a steady state (5-10 min). Figure 2D shows the effects on the HVA current of sequential applications of nimodipine,
Cd2+ was less effective at blocking LVA currents
At higher concentrations cadmium (Cd2+) is a nonselective Ca2+-channel blocker, but at lower concentrations LVA currents have shown less susceptibility than HVA currents (Ozawa et al., 1989The effect of different concentrations of Cd2+ on Ca2+ currents is shown in Figure 3. Part A compares current traces taken in the presence of control, 10, 100, and 500 µ Cd2+. At each concentration, Cd2+ demonstrated a stronger block of the HVA current. For example, some LVA current was spared at concentrations sufficient to eliminate the HVA current (see the 100 µ traces). The two components of the LVA current shared a similar sensitivity to Cd2+. In Figure 3B, the amplitudes of the LVA difference, LVA sustained, and HVA currents are plotted over time. Time zero is the onset of whole-cell recording (break-in). Ca2+ currents tended to run up for ~10 min and then run down over the rest of the experiment. We typically waited 15 min after breaking-in before starting drug applications. The rate of rundown differed among the current components. HVA currents ran down the fastest, whereas the LVA difference component ran down slowest. On average, the HVA current ran down to half of its original amplitude (determined 15 min after break-in) over the next
2000 sec. In comparison, the LVA sustained and LVA difference components ran down to half of their original amplitude over
Fig. 3. Cd2+ was less effective at blocking LVA currents. A, Current traces taken in the presence of control, 10, 100, and 500 µ Cd2+. The top set of traces shows LVA currents. Bottom traces show the effects of the same applications on HVA currents. For the HVA current, the 100 and 500 µ traces are indistinguishable. Note the initial transient in the 10 µ trace (arrow), indicating time-dependent equilibration of the block to the new membrane potential. B, Time course of current component amplitudes from the same cell as in A. The amplitude of the LVA difference component (top), LVA sustained component (middle), and HVA peak (bottom) are plotted as a function of time, with 0 corresponding to the start of whole-cell recording. Dotted lines during the 100 µ exposure demonstrate how the baseline was extrapolated for measurements. C, Dose-response relationship for Cd2+ for the measured current components. Current amplitudes are normalized to the estimated baseline amplitude. The percent of the control amplitude of the LVA difference (), LVA sustained (
) are plotted as a function of Cd2+ concentration. Error bars in all figures represent SEM. The HVA current was much more sensitive (IC50 < 1 µ) to Cd2+ than the two LVA current components, which were equally sensitive (IC50
[View Larger Version of this Image (24K GIF file)]
Although the block was less, we cannot conclude that Cd2+ has a lower affinity for LVA channels. Because HVA currents were assayed at 0 mV but LVA currents were measured at
Ni2+ reduced the inactivating component of the LVA current
Nickel (Ni2+) is the most commonly used antagonist for T-type channels and has been used to probe the physiological function of T-type channels (Hagiwara et al., 1988The effect of different concentrations of Ni2+ on Ca2+ currents is shown in Figure 4. Part A compares current traces taken in the presence of control, 10, 50, and 500 µ Ni2+. At a given concentration, Ni2+ was most effective at blocking the inactivating component of the LVA current (for example, see the 50 µ trace). Part B plots the amplitudes of the LVA difference (top), LVA sustained (middle), and HVA (bottom) currents over time. Figure 4C summarizes the Ni2+ dose-response of the measured components of the Ca2+ current. The LVA difference component was most sensitive, with 10 µ < IC50 < 50 µ. The sustained LVA component and the HVA current were less sensitive. Both had a 100 µ < IC50 < 500 µ. Concentrations of Ni2+ sufficient to eliminate the transient component (>100 µ) markedly reduced other components of the Ca2+ current. We conclude that Ni2+ preferentially blocks channels underlying the LVA difference component, although other channel types may also be inhibited by Ni2+.
Fig. 4. Ni2+ preferentially inhibited the LVA difference component. A, Current traces taken in the presence of control, 10, 50, and 500 µ Ni2+. The top set of traces shows LVA currents. Bottom traces show the effects of the same applications on HVA currents. At a given concentration, Ni2+ was most effective at blocking the transient component of the LVA current (for example, see the 50 µ trace). B, Time course of current component amplitudes from the same cell in A. The amplitude of the LVA difference component (top), LVA sustained component (middle), and HVA peak (bottom) are plotted as a function of time. Dotted lines during the 50 µ exposure demonstrate how the baseline was extrapolated for measurements. C, Dose-response relationship for Ni2+ for the measured current components. Effects on LVA difference (
[View Larger Version of this Image (23K GIF file)]
Amiloride, phenytoin, and ethosuximide affected the LVA current differently
Amiloride blocks T-type channels in hippocampal neurons (Takahashi et al., 1989
Fig. 5. Effects of putative T-channel blockers. A, Traces showing the effects of amiloride (250 µ). LVA currents are shown on the left. HVA currents from the same application are on the right. Traces are labeled as control (c), drug (d), or wash (w). The inactivating component of the LVA current was affected most strongly by amiloride. B, Effects of phenytoin (100 µ). Phenytoin most strongly blocked the LVA sustained current. C, Effect of ethosuximide (250 µ). No current components were affected. D, Summary data for putative T-channel blockers. The bar height indicates the amplitude of the current as a percentage of the control amplitude. Bars represent LVA difference (black), LVA sustained (gray), and HVA (white) current components. Amiloride, either alone or with Ni2+, most strongly blocked the LVA difference component. The amplitude of the current (as a percent of the control value) in the presence of drug was 250 µ: LVA difference 51%, LVA sustained 77% (n = 5), HVA 95% (n = 7); amiloride (250 µ) + Ni2+ (50 µ): LVA difference 24%, LVA sustained 70%, HVA 75% (n = 3). Phenytoin (100 µ) affected all components but had its greatest effect on the LVA sustained component (LVA difference 84%, LVA sustained 62%, HVA 88%; n = 6). Ethosuximide, at concentrations up to 1 m, had no effect on any current component. The amplitude of the current in the presence of ethosuximide was 250 µ: LVA difference 96%, LVA sustained 103%, HVA 98% (n = 3); 1 m: LVA difference 92%, LVA sustained 106%, HVA 96% (n = 3).
[View Larger Version of this Image (32K GIF file)]
Phenytoin (diphenylhydantoin) inhibits LVA currents in cultured hippocampal neurons (Yaari et al., 1987
Ethosuximide partially blocks LVA currents in thalamic neurons, and this action is postulated to underlie its anticonvulsant action in thalamic seizures (Coulter et al., 1989
Voltage dependence of T-type Ca2+ channel inactivation
The pharmacological profile of the inactivating LVA current suggests that it results from the openings of T-type Ca2+ channels. We wondered whether the sustained LVA current could be explained by a persistent activation of T-type channels. Steady-state inactivation of T-type channels was determined by measuring the amplitude of the difference component as a function of holding potential. Figure 6A illustrates a typical experiment. Steps to
Fig. 6. Steady-state inactivation of T-type Ca2+ channels. A, Traces showing the dependence of LVA currents on the holding potential. The membrane potential was stepped to
[View Larger Version of this Image (13K GIF file)]
The resulting curve suggests few T-type channels are activatable near steady state at
Dihydropyridines modulated the LVA sustained current
While performing the experiments shown in Figure 2D, we observed that nimodipine, a dihydropyridine (DHP) L-type channel antagonist, reduced the amplitude of the LVA-sustained component. Therefore, we further investigated the effects of DHPs on CA3 Ca2+ currents. We used 10 µ nimodipine, because this is a saturating dose in hippocampal neurons (Eliot and Johnston, 1994
Fig. 7. A, Traces showing the effects of nimodipine (10 µ). LVA currents are shown on the left. HVA currents from the same application are on the right. Traces are labeled as control (c) or drug (d). Nimodipine partially inhibited the LVA sustained component without affecting the LVA difference component. The HVA current was also partially reduced. B, Effects of BayK-8644 (1 µ). BayK-8644 potentiated the LVA sustained current and the HVA current, but the LVA difference current was insensitive. C, Summary data for nimodipine and BayK-8644. Amplitudes of each current component during the application are plotted as a fraction of their control values. DHPs had no effect on the LVA difference component, but the LVA sustained component was modulated similarly to the HVA current. Both were reduced by nimodipine and enhanced by BayK [10 µ nimodipine: LVA difference 100%, LVA sustained 64% (n = 8); HVA 72% (n = 20); 1 µ BayK-8644: LVA difference 95%, LVA sustained 134% (n = 3); HVA 113%, (n = 6)]. The block by coapplying Ni2+ (100 µ) and nimodipine (10 µ) was nearly additive (when compared to their individual effects), indicating that they blocked different types of channels [LVA difference 23%, LVA sustained 31% (n = 4); HVA 52% (n = 6)].
[View Larger Version of this Image (24K GIF file)]
We postulated that DHP-sensitive channels contribute to the LVA-sustained current. One prediction is that BayK-8644, a DHP Ca2+ channel agonist, would potentiate the sustained current. Figure 7B shows the effect of 1 µ BayK-8644. BayK increased the amplitude of the sustained current but did not affect the inactivating component of the LVA current. BayK also had the expected effect on the HVA current: potentiation of the peak and slowing of the deactivation (tail) kinetics.
Population data for nimodipine and BayK-8644 are shown in Figure 7C. It is important to note that the LVA transient current was insensitive to nimodipine and BayK. In contrast, the LVA-sustained component was modulated in parallel with the HVA current
reduced by nimodipine and enhanced by BayK. When coapplied, the block of nimodipine (10 µ) and Ni2+ (100 µ) approximated the sum of their individual effects. This suggests that they are blocking separate types of channels. We conclude that activation of DHP-sensitive channels contributes to the sustained LVA current.
Activation of nimodipine-sensitive current
We determined the steady-state activation of the nimodipine-sensitive current in CA3 neurons. In control saline, the sustained current was measured 120 msec into the depolarization for step potentials from
Fig. 8. Activation of nimodipine-sensitive current. A, Example of data used to generate the plot in C. Top traces show currents recorded in control and nimodipine (10 µ) with steps to 0 mV. Bottom trace is the difference of the top traces, representing the nimodipine-sensitive current. The amplitude of the nimodipine-sensitive current was determined for each test potential by measuring the amplitude of the difference current at 120 msec (arrows). B, I-V relations for nimodipine-sensitive and insensitive currents in a single cell. As shown in A, cells were held at
[View Larger Version of this Image (19K GIF file)]
This activation curve was surprisingly similar to that expected for T-type channels (Fig. 6C). One possible explanation is simply that nimodipine is blocking T-type channels. However, nimodipine did not affect the difference component of the LVA current (Fig. 7C). Additionally, we minimized contamination by T-type currents in the analysis by measuring the current amplitude 120 msec into the step pulse. Further, about 28% of the HVA current (assayed at 0 mV) is blocked by nimodipine. This current does not result from the activation of T-type channels, because it is evoked from a holding potential of
We also fit the sustained currents remaining in the presence of nimodipine. The peak of the I-V of the nimodipine-resistant currents was about 10 mV positive to the peak of the nimodipine-sensitive current (see Fig. 8B). As shown in the dotted lines of Figure 8C, a Boltzmann fit to the nimodipine-resistant current reflected this shift, yielding a V1/2 =
Toxins blocked the LVA sustained component
We used Ca2+-channel toxins to further identify the types of channels responsible for the LVA sustained current. Calciseptine is a snake toxin that irreversibly antagonizes L-type Ca2+ currents without affecting N-type or T-type currents in dorsal root ganglion cells (de Weille et al., 1991
Fig. 9. Toxins block the LVA sustained component. A, Effects of the L-channel antagonist calciseptine. LVA currents are shown on the left. HVA currents from the same application are on the right. Traces are labeled as control (c) or drug (d). Calciseptine (5 µ) partially inhibited the LVA sustained and HVA currents but did not affect the LVA difference current. B, Effects of the nonspecific HVA antagonist
[View Larger Version of this Image (29K GIF file)]
We used the snail toxin
Finally, we used the spider toxin
Table 1 summarizes the pharmacological results of this study. The differential pharmacology of the LVA current is emphasized by grouping drugs according to their selectivity for the LVA difference or sustained component.
Table 1. Pharmacological differences of the LVA current components
LVA HVA Difference Sustained A. Drugs that affect LVA difference current Ni2+ (50 µ) 33 ± 5% (n = 6) 77 ± 3 (6) 89 ± 3 (5) Amiloride (250 µ) 51 ± 3 (5) 77 ± 6 (5) 95 ± 1 (7) Ni2+ + Amil. 24 ± 3 (3) 70 ± 7 (3) 75 ± 4 (5) B. Drugs that affect LVA sustained current Nimodipine (10 µ) 100 ± 5 (8) 64 ± 3 (8) 72 ± 3 (20) BayK-8644 (1 µ) 95 ± 4 (3) 134 ± 9 (3) 113 ± 5 (6) Calciseptine (5 µ) 94 ± 1 (4) 78 ± 2 (4) 79 ± 4 (5) GsTx-SIA (10 µ) 84 ± 5 (3) 74 ± 5 (3) 42 ± 4 (3) Phenytoin (100 µ) 84 ± 6 (6) 62 ± 6 (6) 88 ± 5 (6) C. Drugs that do not discriminate LVA components Cd2+ (100 µ) 50 ± 5 (8) 42 ± 4 (8) 2 ± 1 (9) Ethosuximide (1 m) 92 ± 11 (3) 106 ± 3 (3) 96 ± 0 (3) D600 (100 µ) 42 ± 5 (4) 41 ± 4 (4) 39 ± 4 (3) 98 ± 2 (7) 101 ± 5 (7) 39 ± 6 (10) Drugs are grouped according to whether they preferentially inhibited the LVA difference component (A), the LVA sustained component (B), or did not discriminate between the two LVA components (C). Current component amplitudes in the presence of each drug are expressed as a percentage of the control amplitude; mean ± SEM (n).
DISCUSSION
We recorded LVA and HVA Ca2+ currents in acutely isolated rat hippocampal CA3 pyramidal neurons. Using 2 m Ca2+ as the charge carrier, we recorded two kinetically distinct components of the LVA current: inactivating and noninactivating. We measured the inactivating current as the difference component and the noninactivating current as the sustained component. We determined the pharmacological profile of the two components by using antagonists of LVA and HVA Ca2+ channels.T-type channels underlie the transient component
The voltage dependence, kinetics, and pharmacology of the difference component indicate that it results from activation of T-type Ca2+ channels. T-type channels are abundant on CA3 neurons and would be expected to open with our stimulus to isolate LVA channels (Fisher et al., 1990Usefulness of T-channel blockers
A major goal of this study was to test the usefulness of blockers of T-type Ca2+ channels. To use blockers to dissect the contribution of T-type channels to cellular physiology, it is important to know how much T-type channels can be inhibited without affecting other types of Ca2+ channels.Ni2+ is the most commonly used T-channel antagonist. In CA3 cells, 50 µ Ni2+ blocked approximately two-thirds of the T-type current. However, even this concentration of Ni2+ had some effect on the HVA current, and higher concentrations markedly affected the HVA current. We conclude that concentrations of Ni2+ sufficient to eliminate T-type channels will significantly inhibit other Ca2+ channels as well. Even experiments using lower concentrations of Ni2+ (
50 µ) should be interpreted with the understanding that other types of Ca2+ channels may be partly affected.
Results using amiloride lead to a similar conclusion. Amiloride (250 µ) blocked approximately one-half of the T-type current with a small inhibition of the HVA current. Concentrations of amiloride sufficient to eliminate T-type channels certainly will affect other Ca2+ channels. Moreover, effects of amiloride are not restricted to Ca2+ channels. Indeed, amiloride is most well known as an inhibitor of membrane Na+ flux (Palmer, 1984
Phenytoin has been reported to selectively block T-type channels in cultured hippocampal neurons (Yaari et al., 1987
Ethosuximide, at concentrations up to 1 m, did not affect CA3 Ca2+ currents. This contrasts with the thalamus, in which T-type channels are sensitive to ethosuximide (Coulter et al., 1989
Overall, our results match well with the pharmacology of T-type channels in CA1 cells (Takahashi and Akaike, 1991
Voltage dependence of T-type channels
Our measurements of the voltage dependence of steady-state inactivation for T-type channels in CA3 neurons fit well with those published for CA1 neurons (Takahashi et al., 1991Different channels underlie the two LVA components
The existence of two components to the LVA current raised two general possibilities. The noninactivating component may represent incomplete inactivation of the same channels carrying the transient component. Alternatively, separate channel types could underlie the two components. At least three lines of evidence suggest that more than one type of channel is activated by our subthreshold stimulus. (1) Ni2+ and amiloride were more effective in blocking the difference component than the sustained component. (2) The sustained current was modulated by dihydropyridines, but the difference component was not. (3) Calciseptine,Because the LVA sustained component is partially sensitive to Ni2+ and amiloride, we cannot exclude some contribution of T-type channels to the sustained LVA current. In cranial sensory neurons (Bossu and Feltz, 1986
Hence, T-type channels are not the only Ca2+ channels that warrant the designation ``low-voltage activated.'' Rather, the LVA group comprises the T-type and at least one other type of Ca2+ channel.
Channels underlying the sustained component
Probably the most striking finding in this study was that the LVA current is sensitive to dihydropyridines. The sensitivity of the sustained current to DHPs and the toxin calciseptine indicate that L-type channels may be active at low voltages with physiologic concentrations of external Ca2+. We estimated the voltage dependence of activation of L-type channels by measuring the nimodipine-sensitive current. The largest amplitude of the nimodipine-sensitive current occurred atIt is unlikely that N- or P-type channels contribute to the LVA sustained component, because
Nature of the LVA L-type channels
It is of interest to know if the channels contributing to the LVA sustained component are classic L-type channels or a subpopulation of channels with similar pharmacology but a lower range of activation. Currently, it is difficult to distinguish between these two possibilities. A single Boltzmann adequately fit activation of the nimodipine-sensitive current (Fig. 8C). Hence, it is not necessary to invoke separate populations of L-type channels. The nimodipine-sensitive LVA current can be explained sufficiently as the foot of the activation curve for a homogenous population of L-type channels.Nevertheless, we cannot rule out the possibility that the channels open at
1 subunit for L-type channels. These subunits may undergo alternative RNA splicing (Snutch et al., 1991
Recently, there have been other reports of sustained, nimodipine-sensitive currents at negative potentials (Thibault et al., 1993
Our results make it clear that, in addition to T-type channels, at least one other type of channel can be activated with small depolarizations. L-type channels can be active at potentials much more negative than other HVA channels, where they may contribute to subthreshold Ca2+ signaling.
FOOTNOTES
Received April 18, 1996; revised June 17, 1996; accepted June 18, 1996.
This work was supported by National Institutes of Health Grants MH10473 (R.A.), NS11535, MH44754, and MH48432 (D.J.).
Correspondence should be addressed to Dr. Robert B. Avery, Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
REFERENCES
- Armstrong CM, Matteson DR (1985) Two distinct populations of calcium channels in a clonal line of pituitary cells. Science 227:65-67 .
[Abstract/Free Full Text] - Artalejo CR, Dahmer MK, Perlman RL, Fox AP (1991) Two types of Ca2+ currents are found in bovine chromaffin cells: facilitation is due to the recruitment of one type. J Physiol (Lond) 432:681-707 .
[Abstract/Free Full Text] - Bossu J-L, Feltz A (1986) Inactivation of the low-threshold transient calcium current in rat sensory neurones: evidence for a dual process. J Physiol (Lond) 376:341-357 .
[Abstract/Free Full Text] - Brown AM, Tsuda Y, Wilson DL (1983) A description of activation and conduction in calcium channels based on tail and turn-on current measurements in the snail. J Physiol (Lond) 344:549-583 .
[Abstract/Free Full Text] - Byerly L, Chase PB, Stimers JR (1984) Calcium current activation kinetics in neurones of the snail Lymnaea stagnalis. J Physiol (Lond) 348:187-207 .
[Abstract/Free Full Text] - Carbone E, Lux HD (1984) A low-voltage-activated calcium conductance in embryonic chick sensory neurons. Biophys J 46:413-418 . [Web of Science][Medline]
- Coulter DA, Huguenard JR, Prince DA (1989) Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons. Neurosci Lett 98:74-78 . [Web of Science][Medline]
- Destexhe A, Contreras D, Steriade M, Sejnowski TJ, Huguenard JR (1996) In vivo, in vitro, and computational analysis of dendritic calcium currents in thalamic reticular neurons. J Neurosci 16:169-185 .
[Abstract/Free Full Text] - Eilers J, Augustine GJ, Konnerth A (1995) Subthreshold synaptic Ca2+ signaling in fine dendrites and spines of cerebellar Purkinje neurons. Nature 373:155-158 . [Medline]
- Eliot LS, Johnston D (1994) Multiple components of calcium current in acutely dissociated dentate gyrus granule neurons. J Neurophysiol 72:762-777 .
[Abstract/Free Full Text] - Fisher RE, Gray R, Johnston D (1990) Properties and distribution of single voltage-gated calcium channels in adult hippocampal neurons. J Neurophysiol 64:91-104 .
[Abstract/Free Full Text] - Forti L, Pietrobon D (1993) Functional diversity of L-type calcium channels in rat cerebellar neurons. Neuron 10:437-450 . [Web of Science][Medline]
- Fox AP, Nowycky MC, Tsien RW (1987) Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol (Lond) 394:149-172 .
[Abstract/Free Full Text] - Hablitz JJ, Johnston D (1981) Endogenous nature of spontaneous bursts in hippocampal neurons. Cell Mol Neurobiol 1:325-334 . [Web of Science][Medline]
- Hagiwara N, Irisawa H, Kameyama M (1988) Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells. J Physiol (Lond) 395:233-253 .
[Abstract/Free Full Text] - Herrington J, Lingle CJ (1992) Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells. J Neurophysiol 68:213-232 .
[Abstract/Free Full Text] - Hille B (1992) Modifiers of gating. In: Ionic channels of excitable membranes, , p. 445. Sunderland, MA: SinauerAssociates.
- Hume JR (1985) Comparative interactions of organic Ca2+ channel antagonists with myocardial Ca2+ and K+ channels. J Pharmacol Exp Ther 234:134-140 .
[Abstract/Free Full Text] - Jahnsen H, Llinas R (1984) Ionic basis for the electroresponsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J Physiol (Lond) 349:227-247 .
[Abstract/Free Full Text] - Johnston D, Magee JC, Christie BR, Avery RB (1995) A steady-state, nimodipine-sensitive calcium current active at rest in hippocampal CA1 dendrites. Soc Neurosci Abstr 21:1742.
- Jones SW, Jacobs LS (1990) Dihydropyridine actions on calcium currents of frog sympathetic neurons. J Neurosci 10:2261-2267 . [Abstract]
- Kamiya H (1989) Amiloride suppresses the induction of long-term potentiation in the mossy fiber pathway but not in the commissural/associational pathway of the hippocampal CA3 region. Synapse 3:286-287 . [Web of Science][Medline]
- Kavalali ET, Plummer MR (1994) Selective potentiation of a novel calcium channel in rat hippocampal neurones. J Physiol (Lond) 480:475-484 .
[Abstract/Free Full Text] - Kuo C-C, Bean BP (1994) Slow binding of phenytoin to inactivated sodium channels in rat hippocampal neurons. Mol Pharmacol 46:716-725 . [Abstract]
- Llinás R, Yarom Y (1981) Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol (Lond) 315:569-584 .
[Abstract/Free Full Text] - Magee JC, Johnston D (1995a) Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. Science 268:301-304 .
[Abstract/Free Full Text] - Magee JC, Johnston D (1995b) Characterization of single voltage-gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J Physiol (Lond) 487:67-90 .
[Abstract/Free Full Text] - Magee JC, Christofi G, Miyakawa H, Christie B, Lasser-Ross N, Johnston D (1995) Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons. J Neurophysiol 74:1335-1342 .
[Abstract/Free Full Text] - Marchetti C, Amico C, Usai C (1995) Functional characterization of the effect of nimodipine on the calcium current in rat cerebellar granule cells. J Neurophysiol 73:1169-1180 .
[Abstract/Free Full Text] - Markram H, Sakmann B (1994) Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc Natl Acad Sci USA 91:5207-5211 .
[Abstract/Free Full Text] - Matsuki N, Quandt FN, Eick RET, Yeh JZ (1984) Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells. J Pharmacol Exp Ther 228:523-530 .
[Abstract/Free Full Text] - McDonough SI, Swartz KJ, Mintz IM, Boland LM, Bean BP (1996) Inhibition of calcium channels in rat central and peripheral rat neurons by
[Abstract/Free Full Text] - Mogul DJ, Fox AP (1991) Evidence for multiple types of Ca2+ channels in acutely isolated hippocampal CA3 neurones of the guinea-pig. J Physiol (Lond) 433:259-281 .
[Abstract/Free Full Text] - Niedermeyer E (1990) Phenytoin, other hydantoins, and further derivatives. In: The epilepsies: diagnosis and treatment, , p. 277. Baltimore, MD: Urban and Schwarzenberg.
- Ozawa S, Tsuzuki K, Iino M, Ogura A, Kudo Y (1989) Three types of voltage-dependent calcium current in cultured rat hippocampal neurons. Brain Res 495:329-336 . [Web of Science][Medline]
- Palmer LG (1984) Voltage-dependent block by amiloride and other monovalent cations of apical Na+ channels in the toad urinary bladder. J Membr Biol 80:153-165 . [Web of Science][Medline]
- Piser TM, Lampe RA, Keith RA, Thayer SA (1995)
- Provencher SW (1976) A Fourier method for the analysis of exponential decay curves. Biophys J 16:27-41 . [Web of Science][Medline]
- Regan LJ, Sah DWY, Bean BP (1991) Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and
- Snutch TP, Tomlinson WJ, Leonard JP, Gilbert MM (1991) Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron 7:45-57 . [Web of Science][Medline]
- Takahashi K, Akaike N (1991) Calcium antagonist effects on low-threshold (T-type) calcium current in rat isolated hippocampal CA1 pyramidal neurons. J Pharmacol Exp Ther 256:169-175 .
[Abstract/Free Full Text] - Takahashi K, Wakamori M, Akaike N (1989) Hippocampal CA1 pyramidal cells of rats have four voltage-dependent calcium conductances. Neurosci Lett 104:229-234 . [Web of Science][Medline]
- Takahashi K, Ueno S, Akaike N (1991) Kinetic properties of T-type Ca2+ currents in isolated rat hippocampal CA1 pyramidal neurons. J Neurophysiol 65:148-155 .
[Abstract/Free Full Text] - Tang C-M, Presser F, Morad M (1988) Amiloride selectively blocks the low-threshold (T) calcium channel. Science 240:213-215 .
[Abstract/Free Full Text] - Thibault O, Porter NM, Landfield PW (1993) Low Ba2+ and Ca2+ induce a sustained high probability of repolarization openings of L-type Ca2+ channels in hippocampal neurons: physiological implications. Proc Natl Acad Sci USA 90:11792-11796 .
[Abstract/Free Full Text] - Thompson SM, Wong RKS (1991) Development of calcium current subtypes in isolated rat hippocampal pyramidal cells. J Physiol (Lond) 439:671-689 .
[Abstract/Free Full Text] - Turner TJ, Lampe RA, Dunlap K (1995) Characterization of presynaptic calcium channels with
- de Weille JR, Schweitz J, Maes P, Tartar A, Lazdunski M (1991) Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel. Proc Natl Acad Sci USA 88:2437-2440 .
[Abstract/Free Full Text] - Yaari Y, Hamon B, Lux HD (1987) Development of two types of calcium channels in cultured mammalian hippocampal neurons. Science 235:680-682 .
[Abstract/Free Full Text] - Yatani A, Brown AM (1985) The calcium channel blocker nitrendipine blocks sodium channels in neonatal rat cardiac myocytes. Circ Res 56:868-875 .
[Abstract/Free Full Text] - Zhou W, Jones SW (1995) Surface charge and calcium channel saturation in bullfrog sympathetic neurons. J Gen Physiol 105:441-462 .
[Abstract/Free Full Text]
Copyright ©1996 Society for Neuroscience 0270-6474/1996/165567-16$05.00/0
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