Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons

doi:10.1016/S0024-3205(01)01042-6

Life Sciences

Volume 68, Issues 22–23, 27 April 2001, Pages 2481-2487

https://doi.org/10.1016/S0024-3205(01)01042-6 Get rights and content

Abstract

Many different G protein-coupled receptors modulate the activity of Ca²+ and K⁺ channels in a variety of neuronal types. There are five known subtypes (M₁–M₅) of muscarinic acetylcholine receptors. Knockout mice lacking the M₁, M₂, or M₄ subtypes are studied to determine which receptors mediate modulation of voltage-gated Ca²+ channels in mouse sympathetic neurons. In these cells, muscarinic agonists modulate N- and L-type Ca²+ channels and the M-type K⁺ channel through two distinct, G-protein mediated pathways. The fast and voltage-dependent pathway is lacking in the M₂ receptor knockout mice. The slow and voltage-independent pathway is absent in the M₁ receptor knockout mice. Neither pathway is affected in the M₄ receptor knockout mice. Muscarinic modulation of the M current is absent in the M₁ receptor knockout mice, and can be reconstituted in a heterologous expression system using cloned channels and M₁ receptors. Our results using knockout mice are compared with pharmacological data in the rat.

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Muscarinic function in gene-altered miceIdentification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons

Abstract

Muscarinic function in gene-altered mice
Identification of subtypes of muscarinic receptors that regulate Ca²+ and K⁺ channel activity in sympathetic neurons