Many different G protein-coupled receptors modulate the activity of Ca 2+ and K + channels in a variety of neuronal types. There are five known subtypes (M 1 -M 5 ) of muscarinic acetylcholine receptors. Knockout mice lacking the M 1 , M 2 , or M 4 subtypes are studied to determine which receptors mediate modulation of voltage-gated Ca 2+ channels in mouse sympathetic neurons. In these cells, muscarinic agonists modulate N- and L-type Ca 2+ channels and the M-type K + channel through two distinct, G-protein mediated pathways. The fast and voltage-dependent pathway is lacking in the M 2 receptor knockout mice. The slow and voltage-independent pathway is absent in the M 1 receptor knockout mice. Neither pathway is affected in the M 4 receptor knockout mice. Muscarinic modulation of the M current is absent in the M 1 receptor knockout mice, and can be reconstituted in a heterologous expression system using cloned channels and M 1 receptors. Our results using knockout mice are compared with pharmacological data in the rat.
- Ca channel
- G protein
- M current
- Muscarinic receptor
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)