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Heteromeric Complexes of α5 and/or α7 Subunits: Effects of Calcium and Potential Role in Nicotine‐Induced Presynaptic Facilitation
Author(s) -
GIROD R.,
CRABTREE G.,
ERNSTROM G.,
RAMIREZLATORRE J.,
McGEHEE D.,
TURNER J.,
ROLE L.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11331.x
Subject(s) - homomeric , chemistry , nicotinic agonist , acetylcholine receptor , gating , biophysics , nicotinic acetylcholine receptor , neuroscience , ionotropic effect , nicotine , protein subunit , voltage dependent calcium channel , microbiology and biotechnology , receptor , calcium , biology , biochemistry , glutamate receptor , organic chemistry , gene
Nicotine alters a broad spectrum of behaviors, including attention, arousal, anxiety, and memory. The cellular physiology of nicotine is comparably diverse: nicotine interacts with an array of ionotropic receptors whose gating can lead to direct depolarization of neurons or to an indirect modulation of neuronal excitability by presynaptic facilitation. Furthermore, as many laboratories have shown, the α‐ and β‐type subunits that comprise neuronal nicotinic acetylcholine receptors (nAChRs) are encoded by multiple, homologous genes, yielding at least seven α and three β subunits, distinct in primary sequence. nAChRs that differ in subunit composition differ in pharmacology, conductance, and kinetics as well as in their permeability to and modulation by calcium. We will first discuss recent studies on the biophysics of a special (peculiar?) subset of nAChRs, focusing on heteromeric nAChRs comprised of α4β2 ±α5 or α7 ±β2 and α5. These nAChR channel subtypes are potently and differentially modulated by changes in intracellular calcium ([Ca]). Thus, the P o , τ o , and desensitization kinetics of α4β2 channels are altered by changes in [Ca] int from 0 to 50 μM; nAChRs that include the α5 subunit are oppositely regulated. Mutagenesis of specific residues within the M1 to M2 domain of α4, β2, and α5 suggest a possible Ca binding “pocket.” The assembly of functional nAChRs that include α5 and/or α7 and the potential role of these novel heteromeric complexes in presynaptic facilitation will also be presented.