A functional AMPA receptor–calcium channel complex in the postsynaptic membrane

Abstract

Ca 2؉ channels play critical roles in the regulation of synaptic activity. In contrast to the well established function of voltageactivated Ca 2؉ channels in the presynaptic membrane for neurotransmitter release, some studies are just beginning to elucidate the functions of the Ca 2؉ channels in the postsynaptic membrane.In this study, we demonstrated the functional association of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors with the neuronal Ca 2؉ channels. A series of biochemical studies showed the specific association of Ca v2.1 (␣1A-class) and Ca v2.2 (␣1B-class) with AMPA receptors in the postsynaptic membrane. Our electrophysiological and Ca 2؉ imaging analyses of recombinant Ca v2.1 and AMPA receptors also showed functional coupling of the two channels. Considering the critical roles of postsynaptic intracellular concentration of Ca 2؉ ([Ca 2؉ ]i) increase and AMPA receptor trafficking for long-term potentiation (LTP) and long-term depression (LTD), the functional association of Ca 2؉ channels with the AMPA receptors may provide new insights into the mechanism of synaptic plasticity.voltage-activated Ca 2ϩ channel ͉ stargazin ͉ glutamate receptor ͉ synaptic plasticity ͉ postsynaptic density N eurotransmitter-mediated communication between a presynaptic and a postsynaptic membrane is a fundamental neurophysiological phenomenon. The precise organization and dynamic change of presynaptic and postsynaptic protein components underlies the physiological regulation of synaptic efficacy. The study of the organization and dynamics of synaptic proteins is the key to our understanding of synaptic plasticity, neuronal development, and some neurological disorders.The ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor is one of the major types of glutamate receptors (GluRs) mediating neurotransmission in the excitatory postsynaptic membrane. Activity-dependent trafficking of AMPA receptors in and out of the postsynaptic membrane is one of the key mechanisms for synaptic plasticity such as long-term potentiation (LTP) and long-term depression. Although recent studies have identified several postsynaptic proteins that interact with the AMPA receptor C terminus and are potentially involved in AMPA receptor trafficking, the precise mechanism for the modulation of AMPA receptors trafficking in the postsynaptic membrane is still not clear (1).Voltage-activated Ca 2ϩ channels function in many fundamental physiological processes, including neurotransmission, muscle contraction, intracellular signaling, hormone secretion, and development. The function of voltage-activated Ca 2ϩ channels (called Ca 2ϩ channels or Ca v hereafter) for neurotransmission in the presynaptic membrane has been intensively studied because the Ca 2ϩ channel is a key player in the coupling of electric and chemical signals in presynapses. In addition to the presynaptic function, postsynaptic function of Ca 2ϩ channels is beginning to be revealed through recent biophysical studies. Induction of hippocampal mossy fiber LTP ...

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

“…The γ 2 calcium channel subunit 'stargazin' has been likened to an auxillary subunit of the AMPAR and is importantly involved in AMPAR trafficking and function (Tomita et al, 2005;Vandenberghe et al, 2005;Tomita et al, 2006). More recently, neuronal calcium channels have been shown to reside in a multimolecular complex including the GluR1 and GluR2/3 AMPA receptor subunits which, in turn, co-immunoprecipitate with the pore forming α1 subunit CAv2.1 (Kang et al, 2006). These findings point to the speculative possibility that integrin signaling may regulate AMPAR coupling with calcium channel proteins (γ 2 , CAv2.2, and maybe others) and thereby strengthen the influence of these glutamate receptors over calcium channel gating.…”

Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

“…Biochemistry of Native Neuronal VDCC Complexes-To obtain the crude synaptic membrane (CSM) fraction, subcellular fractionation was performed based on a previously described method (24), with slight modification. Whole mouse brains (8 g) were homogenized in a homogenization buffer containing 4 mM HEPES, 0.32 M sucrose, 5 mM EDTA, 5 mM EGTA, and protease inhibitors (pH 7.4).…”

Glutamate-induced Calcium Transients in Rat Neurons of the Dorsal Motor Nucleus of the Vagus

“…21 A recent study demonstrated the physical and functional association of AMPA receptors and voltagegated Ca 2+ channels in a complex with scaffolding proteins in brain tissue. 19 As prior studies have demonstrated predominantly GluR2-containing AMPA receptors in the DMNV, which are generally Ca 2+ -impermeable and undergo rapid desensitization, the results of the present study suggest a functional association between AMPA receptors and T-type Ca 2+ channels.…”

“…Because most AMPA receptors are Ca 2+ -impermeable, and a functional association has been shown to voltagegated Ca 2+ channels 18,19 , the next series of experiments sought to determine if any subtype of Ca 2+ channels may be involved. The three major subtypes are T-type, L-type, and N-type Ca 2+ channels.…”