Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca2+

doi:10.1016/j.ceca.2010.01.004

Cell Calcium

Volume 47, Issue 4, April 2010, Pages 326-338

https://doi.org/10.1016/j.ceca.2010.01.004 Get rights and content

Abstract

The presynaptic Ca²⁺ signal, which triggers vesicle release, disperses to a broadly distributed residual [Ca²⁺] ([Ca²⁺]_res) that plays an important role in synaptic plasticity. We have previously reported a slowing in the decay timecourse of [Ca²⁺]_res during the second of paired pulses. In this study, we investigated the contributions of organelle and plasma membrane Ca²⁺ flux pathways to the reduction of effectiveness of [Ca²⁺]_res clearance during short-term plasticity in Schaffer collateral terminals in the CA1 field of the hippocampus. We show that the slowed decay timecourse is mainly the result of a transport-dependent Ca²⁺ clearance process; that presynaptic caffeine-sensitive Ca²⁺ stores are not functionally loaded in the unstimulated terminal, but that these stores can effectively take up Ca²⁺ even during high frequency trains of stimuli; and that a rate limiting step of sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) kinetics following the first pulse is responsible for a large portion of the observed slowing of [Ca²⁺]_res clearance during the second pulse. We were able to accurately fit our [Ca²⁺]_res data with a kinetic model based on these observations and this model predicted a reduction in availability of unbound SERCA during paired pulses, but no saturation of Ca²⁺ buffer in the endoplasmic reticulum.

Introduction

Following a presynaptic action potential, there is a rapid rise of [Ca²⁺] in the immediate vicinity of Ca²⁺ channels that triggers release of vesicles docked within this microdomain [1]. This presynaptic Ca²⁺ signal ([Ca²⁺]_pre) then disperses by diffusion and buffering to produce a residual [Ca²⁺] ([Ca²⁺]_res) that decays over the course of tens to hundreds of milliseconds. Presynaptic [Ca²⁺]_res, although at a lower concentration than that necessary for vesicular release, plays a modulatory role that is important in synaptic plasticity [2], [3] and has been implicated as a basis for working memory storage [4]. Thus, the duration of the [Ca²⁺]_res signal is a crucial determinant of the dynamic properties of synaptic transmission.

In a previous study [5], we reported that the decay timecourse of [Ca²⁺]_res is significantly slowed during the second of paired pulses under conditions where short-term synaptic plasticity is observed. In this study, we have investigated those mechanisms that could alter the decay timecourse of [Ca²⁺]_res and hence influence the efficacy of synaptic plasticity. The predominant pathways that determine this timecourse are: (1) entry via voltage-gated Ca²⁺ channels (VGCCs); (2) passive diffusion or buffering; (3) Ca²⁺-dependent Ca²⁺ release (CICR) through ryanodine receptors in the endoplasmic reticulum (ER); (4) uptake into the ER by the sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA); (5) extrusion across the plasma membrane by either the plasma membrane Na/Ca exchanger (NCX) or the plasma membrane Ca²⁺-ATPase (PMCA); and (6) uptake into mitochondria by the mitochondrial Ca²⁺ uniporter (MCU) [6], [7]. Contributions to the timecourse of [Ca²⁺]_res by presynaptic Ca²⁺ buffers and by uptake and release from the ER have been an important focus in previous studies of the involvement of [Ca²⁺]_res in short-term plasticity.

Ca²⁺ buffering by endogenous and exogenously introduced buffers is a ubiquitous passive influence on the dispersion of the Ca²⁺ microdomain and on the timecourse of [Ca²⁺]_res [8]. In addition, saturation of these buffers can make an important contribution to short-term facilitation in some presynaptic terminals, although its contribution appears to be minimal in the Schaffer collateral terminals in the CA1 subfield of the hippocampus [5], [9]. Intracellular Ca²⁺ stores play a crucial role in many facets of neuronal function including synaptic plasticity [10]. Uptake of Ca²⁺ into the presynaptic ER and CICR from these Ca²⁺ stores provides a potentially important modulatory mechanism for neurotransmitter release, although the contribution of presynaptic Ca²⁺ stores to synaptic plasticity depends on the stimulus conditions and the specific synaptic terminal involved. For instance, there is a clear indication of Ca²⁺ stores involvement in long-term synaptic plasticity in the hippocampus including long-term potentiation (LTP) [11] and long-term depression (LTD) [12] and this is consistent with the finding that Ca²⁺ stores make a significant contribution to [Ca²⁺]_res following trains of presynaptic action potentials [13]. The degree of involvement of presynaptic Ca²⁺ stores in short-term plasticity appears to be dependent on the specific synapse type. Thus, mossy fiber terminals in the CA3 hippocampal subfield exhibit CICR-dependent short-term facilitation [14], while other synapses of these fibers do not exhibit the same CICR-dependent mechanism [15]. Additionally, CICR has been found to have no involvement in short-term plasticity in Schaffer collateral terminals on CA1 pyramidal neurons in young rats [16], although another study of these same synapses found CICR involvement in short-term plasticity of functional, but not silent synapses [17].

In this study, we have investigated the contributions of VGCCs, CICR, SERCA, NCX, PMCA, and MCU to the timecourse of [Ca²⁺]_res. We have focused primarily on the slow component of [Ca²⁺]_res decay, since this component reflects [Ca²⁺]_res clearance processes, which occur on the time scale of short-term synaptic plasticity. We show that there is a slowing of the decay timecourse of [Ca²⁺]_res during the second of paired pulses that results from the decrease of a transport-dependent [Ca²⁺]_pre clearance process. Presynaptic caffeine-sensitive Ca²⁺ stores do not contain measurable Ca²⁺ in the unstimulated presynaptic terminal, although these stores can take up [Ca²⁺]_pre during high frequency trains of stimuli. We find a minimal contribution of VGCCs, NCX, PMCA, or MCU in the observed difference of [Ca²⁺]_res decay timecourse between the first and second of paired pulses. However, a limitation of the rate of the SERCA pump following the first presynaptic stimulus is responsible for a large portion of the observed slowing of [Ca²⁺]_res decay. Our kinetic modeling studies are consistent with a major role for SERCA and a significant capacity for ER Ca²⁺ storage during [Ca²⁺]_pre clearance in Schaffer collateral terminals. Furthermore, SERCA clearance of [Ca²⁺]_res appears to be an important contributory factor in the genesis to short-term plasticity.

Section snippets

Slice preparation and field potential recordings

Experiments were performed in coronal hippocampal slices from approximately 50 day-old Sprague-Dawley rats as previously described [5]. Briefly, animals were deeply anesthetized with an i.p. injection of 250 mg/kg ketamine, brains were rapidly removed, and slices were cut at 300 μm with a vibroslicer (Pelco 101, St. Louis, MO) in an ice bath with a cutting solution containing (in mM): 220 sucrose, 3 KCl, 1.2 NaH₂PO₄, 26 NaHCO₃, 12 MgSO₄, 0.2 CaCl₂, 10 glucose, and 0.01 mg/ml ketamine equilibrated

Results

The mechanisms responsible for the regulation of presynaptic [Ca²⁺]_res, have been well characterized in certain specialized synapses, but they are less well understood in the more representative small presynaptic terminals of the CNS [23]. We therefore measured [Ca²⁺]_res during paired stimuli at a 50 ms interpulse interval in Schaffer collateral terminals in stratum radiatum of the CA1subfield of the hippocampus. This interpulse interval was selected because it elicits a form of short-term

Discussion

In a previous study of the role of Ca²⁺ dynamics in governing short-term facilitation, we showed that the ΔR2 ∫ΔF/F₀ was increased over P1 ∫ΔF/F₀ and that this increased presynaptic [Ca²⁺]_res signal was due largely to an increase in τ_s for ΔF/F₀ decay [5]. We proposed that this was indicative of changes in the buffering, sequestering, or extrusion of Ca²⁺ in the presynaptic terminals and designed these studies to investigate contributions from these mechanisms. In order to assess the

Acknowledgements

The authors would like to thank Fernando Valenzuela, Bill Shuttleworth, and Michael Wilson for critically reading this manuscript and William Matthews for computer support. This work was supported by NIH grants R01-MH07386 to LDP and R01-MH48989 to Michael Wilson for financial support of CSS.

References (76)

E. Neher et al.
Multiple roles of calcium ions in the regulation of neurotransmitter release
Neuron
(2008)
W.A. Catterall et al.
Calcium channel regulation and presynaptic plasticity
Neuron
(2008)
M. Blatow et al.
Ca²⁺ buffer saturation underlies paired pulse facilitation in calbindin-D28k-containing terminals
Neuron
(2003)
M.J. Berridge
Neuronal calcium signaling
Neuron
(1998)
S.E. Lauri et al.
A role for Ca²⁺ stores in kainate receptor-dependent synaptic facilitation and LTP at mossy fiber synapses in the hippocampus
Neuron
(2003)
N.J. Emptage et al.
Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca²⁺ entry, and spontaneous transmitter release
Neuron
(2001)
W.G. Regehr et al.
Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice
J. Neurosci. Methods
(1991)
S.R. Sinha et al.
Presynaptic calcium dynamics and transmitter release evoked by single action potentials at mammalian central synapses
Biophys. J.
(1997)
W.G. Regehr et al.
Calcium transients in cerebellar granule cell presynaptic terminals
Biophys. J.
(1995)
L. McGuinness et al.
The lysosome or lysosome-related organelle may serve as a Ca²⁺ store in the boutons of hippocampal pyramidal cells
Neuropharmacology
(2007)

F. Fuchs

Ion exchange properties of the calcium receptor site of troponin

Biochim. Biophys. Acta

(1971)

R. Bouchard et al.

Presence and functional significance of presynaptic ryanodine receptors

Prog. Neurobiol.

(2003)

S.M. Fitzjohn et al.

Calcium stores and synaptic plasticity

Cell Calcium

(2002)

L.G. Wu et al.

Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus

Neuron

(1994)

M. Muschol et al.

Caffeine interaction with fluorescent calcium indicator dyes

Biophys. J.

(1999)

S.S. Zakharenko et al.

Presynaptic BDNF required for a presynaptic but not postsynaptic component of LTP at hippocampal CA1-CA3 synapses

Neuron

(2003)

R. Udagawa et al.

Blocking L-type calcium channels enhances long-term depression induced by low-frequency stimulation at hippocampal CA1 synapses

Brain Res.

(2006)

A. Minelli et al.

Cellular and subcellular localization of Na⁺-Ca²⁺ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat

Cell Calcium

(2007)

X.F. Li et al.

Importance of K⁺-dependent Na⁺/Ca²⁺-exchanger 2, NCKX2, in motor learning and memory

J. Biol. Chem.

(2006)

M. Brini

Ca(2+) signalling in mitochondria: mechanism and role in physiology and pathology

Cell Calcium

(2003)

N. Burnashev et al.

Presynaptic Ca²⁺ dynamics, Ca²⁺ buffers and synaptic efficacy

Cell Calcium

(2005)

N. Solovyova et al.

Monitoring of free calcium in the neuronal endoplasmic reticulum: an overview of modern approaches

J. Neurosci. Methods

(2002)

E.R. Higgins et al.

A buffering SERCA pump in models of calcium dynamics

Biophys. J.

(2006)

H.L. Baker et al.

A mathematical model predicts that calreticulin interacts with the endoplasmic reticulum Ca²⁺-ATPase

Biophys. J.

(2002)

L. Dode et al.

Dissection of the functional differences between sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) 1 and 3 isoforms by steady-state and transient kinetic analyses

J. Biol. Chem.

(2002)

M.S. Jafri et al.

On the roles of Ca²⁺ diffusion, Ca²⁺ buffers, and the endoplasmic reticulum in IP3-induced Ca²⁺ waves

Biophys. J.

(1995)

R.S. Zucker et al.

Short-term synaptic plasticity

Annu. Rev. Physiol.

(2002)

G. Mongillo et al.

Synaptic theory of working memory

Science

(2008)

A.R. Schiess et al.

Neurosteroid-induced enhancement of short-term facilitation involves a component downstream from presynaptic calcium in hippocampal slices

J. Physiol.

(2006)

D.A. Rusakov

Ca²⁺-dependent mechanisms of presynaptic control at central synapses

Neuroscientist

(2006)

M.H. Kim et al.

Interplay between Na⁺/Ca²⁺ exchangers and mitochondria in Ca²⁺ clearance at the calyx of Held

J. Neurosci.

(2005)

E. Neher et al.

Calcium gradients and buffers in bovine chromaffin cells

J. Physiol.

(1992)

V.K. Unni et al.

Calcium release from presynaptic ryanodine-sensitive stores is required for long-term depression at hippocampal CA3-CA3 pyramidal neuron synapses

J. Neurosci.

(2004)

R. Scott et al.

Main determinants of presynaptic Ca²⁺ dynamics at individual mossy fiber-CA3 pyramidal cell synapses

J. Neurosci.

(2006)

R. Scott et al.

Target-cell specificity of kainate autoreceptor and Ca²⁺-store-dependent short-term plasticity at hippocampal mossy fiber synapses

J. Neurosci.

(2008)

A.G. Carter et al.

Assessing the role of calcium-induced calcium release in short-term presynaptic plasticity at excitatory central synapses

J. Neurosci.

(2002)

C. Cabezas et al.

Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses

J. Neurophysiol.

(2006)

P.P. Atluri et al.

Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse

J. Neurosci.

(1996)

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Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca2+

Abstract

Introduction

Section snippets

Slice preparation and field potential recordings

Results

Discussion

Acknowledgements

Neuron

Neuron

Neuron

Neuron

Neuron

Neuron

J. Neurosci. Methods

Biophys. J.

Biophys. J.

Neuropharmacology

Biochim. Biophys. Acta

Prog. Neurobiol.

Cell Calcium

Neuron

Biophys. J.

Neuron

Brain Res.

Cell Calcium

J. Biol. Chem.

Cell Calcium

Cell Calcium

J. Neurosci. Methods

Biophys. J.

Biophys. J.

J. Biol. Chem.

Biophys. J.

Short-term synaptic plasticity

Annu. Rev. Physiol.

Synaptic theory of working memory

Science

Neurosteroid-induced enhancement of short-term facilitation involves a component downstream from presynaptic calcium in hippocampal slices

J. Physiol.

Ca2+-dependent mechanisms of presynaptic control at central synapses

Neuroscientist

Interplay between Na+/Ca2+ exchangers and mitochondria in Ca2+ clearance at the calyx of Held

J. Neurosci.

Calcium gradients and buffers in bovine chromaffin cells

J. Physiol.

Calcium release from presynaptic ryanodine-sensitive stores is required for long-term depression at hippocampal CA3-CA3 pyramidal neuron synapses

J. Neurosci.

Main determinants of presynaptic Ca2+ dynamics at individual mossy fiber-CA3 pyramidal cell synapses

J. Neurosci.

Target-cell specificity of kainate autoreceptor and Ca2+-store-dependent short-term plasticity at hippocampal mossy fiber synapses

J. Neurosci.

Assessing the role of calcium-induced calcium release in short-term presynaptic plasticity at excitatory central synapses

J. Neurosci.

Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses

J. Neurophysiol.

Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse

J. Neurosci.

Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca²⁺

Ca²⁺-dependent mechanisms of presynaptic control at central synapses

Interplay between Na⁺/Ca²⁺ exchangers and mitochondria in Ca²⁺ clearance at the calyx of Held

Main determinants of presynaptic Ca²⁺ dynamics at individual mossy fiber-CA3 pyramidal cell synapses

Target-cell specificity of kainate autoreceptor and Ca²⁺-store-dependent short-term plasticity at hippocampal mossy fiber synapses