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

doi:10.1073/pnas.0601289103

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

*Howard Hughes Medical Institute and Departments of Physiology and Biophysics, Internal Medicine, and Neurology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242; and
^†Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan

Contributed by Kevin P. Campbell, February 16, 2006

Abstract

Ca²⁺ channels play critical roles in the regulation of synaptic activity. In contrast to the well established function of voltage-activated Ca²⁺ channels in the presynaptic membrane for neurotransmitter release, some studies are just beginning to elucidate the functions of the Ca²⁺ channels in the postsynaptic membrane. In this study, we demonstrated the functional association of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors with the neuronal Ca²⁺ channels. A series of biochemical studies showed the specific association of Ca_v2.1 (α_1A-class) and Ca_v2.2 (α_1B-class) with AMPA receptors in the postsynaptic membrane. Our electrophysiological and Ca²⁺ 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 Ca²⁺ ([Ca²⁺]_i) increase and AMPA receptor trafficking for long-term potentiation (LTP) and long-term depression (LTD), the functional association of Ca²⁺ channels with the AMPA receptors may provide new insights into the mechanism of synaptic plasticity.

Footnotes

^‡To whom correspondence should be addressed. E-mail: kevin-campbell{at}uiowa.edu
Author contributions: M.-G.K., C.-C.C., Y.M., and K.P.C. designed research; M.-G.K., M.W., and Y.H. performed research; M.-G.K., C.-C.C., M.W., Y.H., Y.M., and K.P.C. analyzed data; and M.-G.K. and K.P.C. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

Abbreviations:

AMPA,

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate;

PSD,

postsynaptic density;

WGA,

wheat germ agglutinin;

HEK,

human embryonic kidney;

GluR,

glutamate receptor