The Coupling of the Neuronal Muscarinic Receptor to Responses

Abstract

Muscarinic acetylcholine receptors are plasma membrane proteins that bind the neurotransmitter acetylcholine and by their conformational changes elicit spe­ cific biological events within cells. They are pharmacologically defined by their binding selectivity for a specific class of drugs, among which are the agonists muscarine and oxotremorine and the various atropine-like antagonists. Muscarinic receptors mediate various types of responses in cardiac muscle, in numerous smooth muscles, in exocrine glands, throughout the peripheral and central nervous system, and in some kinds of cultured nerve cells. Usually two or three subtypes of muscarinic receptors exist, distinguished by their relative binding affinity for agonists (I). Though the types of biological responses among these tissues are varied. the respective proteins that bind the agonist appear to be similar or identical in binding properties and molecular size. It is probably their coupling to unique tissue-specific effectors that gives rise to varied responses. Responses mediated by muscarinic receptors are slow in onset and develop­ ment and thus are distinctly different from nicotinic responses, but like nicotin­ ic responses they can desensitize. In the brain, where the muscarinic receptor is the predominant cholinergic receptor, its activation can lead to either excitation or inhibition of neurons (2). In the cerebral cortex, for example, pyramidal cells become depolarized from decreases in potassium (K+) conductance (3),