QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 3, 2007, 27(40):10785-10796; doi:10.1523/JNEUROSCI.0935-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Jackson, A. C. Articles by Bean, B. P. Search for Related Content PubMed PubMed Citation Articles by Jackson, A. C. Articles by Bean, B. P.

 Previous Article  |  Next Article 

Cellular/Molecular
State-Dependent Enhancement of Subthreshold A-Type Potassium Current by 4-Aminopyridine in Tuberomammillary Nucleus Neurons

Alexander C. Jackson and Bruce P. Bean

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Bruce P. Bean, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: bruce_bean{at}hms.harvard.edu

A-type potassium current (I_A) both activates and inactivates at subthreshold voltages. We asked whether there is steady-state I_A at subthreshold voltages, using dissociated mouse tuberomammillary nucleus neurons, pacemaking neurons with large I_A currents in which subthreshold I_A might regulate firing frequency. With slow depolarizing voltage ramps (20 mV/s), there was no discernible component of steady-state outward current in the range of –70 to –40 mV. However, faster ramps of 50–100 mV/s, similar to the rate of spontaneous depolarization during pacemaking, did evoke subthreshold outward currents. Ramp-evoked current at subthreshold voltages was unaffected by 10 mM tetraethylammonium and likely represents I_A, because its voltage dependence overlaps that of I_A activation (midpoint near –44 mV) and inactivation (midpoint near –85 mV). However, although 4-aminopyridine (4-AP) inhibited peak I_A activated by step depolarizations as expected (IC₅₀, 1 mM), ramp-evoked current was instead dramatically enhanced (current at –40 mV evoked by 50 mV/s ramp enhanced >15-fold by 10 mM 4-AP). In cell-attached recordings of spontaneous pacemaking, 10 mM 4-AP slowed rather than speeded firing, consistent with enhancement of subthreshold I_A. Also consistent with such enhancement, 4-AP also greatly increased the latency to first spike after long hyperpolarizations. The striking enhancement of I_A during depolarizing ramps can be explained by a model in which 4-AP binds tightly to closed channels but must unbind before channels can inactivate. Thus, the state dependence of 4-AP binding to the channels underlying I_A can result in effects on firing patterns opposite to those expected from simple block of I_A.

Key words: I_A; I_K; spontaneous firing; pacemaking; spike latency; Kv4.2

---

Received March 1, 2007; revised Aug. 9, 2007; accepted Aug. 19, 2007.

Correspondence should be addressed to Bruce P. Bean, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: bruce_bean{at}hms.harvard.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2007 27: i. [Full Text]  

This article has been cited by other articles:

				X. Liu and C. Chen Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse J Neurophysiol, February 1, 2008; 99(2): 629 - 643. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help