Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons
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.
Shapiro, Mark S., Jesus Gomeza, Susan E. Hamilton, et al. 2001. "Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons." Life Sciences 68(22-23): 2481-2487.
Muscarinic receptor, G protein, Ca2+ channel, M current