Identification of subtypes of muscarinic receptors that regulate Ca 2+ and K + channel activity in sympathetic neurons

Mark S. Shapiro, Jesus Gomeza, Susan E. Hamilton, Bertil Hille, Michael D. Loose, Neil M. Nathanson, John P. Roche, Jürgen Wess

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2481-2487
Number of pages7
JournalLife Sciences
Volume68
Issue number22-23
DOIs
StatePublished - Apr 27 2001

Keywords

  • Ca channel
  • G protein
  • M current
  • Muscarinic receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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