Single channel studies of inward rectifier potassium channel regulation by muscarinic acetylcholine receptors.
Negative regulation of the heartbeat rate involves the activation of an inwardly rectifying potassium current (I(KACh)) by G protein-coupled receptors such as the m2 muscarinic acetylcholine receptor. Recent studies have shown that this process involves the direct binding of G(betagamma) subunits to the NH(2)- and COOH-terminal cytoplasmic domains of the proteins termed GIRK1 and GIRK4 (Kir3.1 and Kir3.4/CIR), which mediate I(KACh). Because of the very low basal activity of native I(KACh), it has been difficult to determine the single channel effect of G(betagamma) subunit binding on I(KACh) activity. Through analysis of a novel G protein-activated chimeric inward rectifier channel that displays increased basal activity relative to I(KACh), we find that single channel activation can be explained by a G protein-dependent shift in the equilibrium of open channel transitions in favor of a bursting state of channel activity over a long-lived closed state.
Bard
J
J
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. bard@bbri.org
Kunkel
M T
MT
Peralta
E G
EG
D000818:Animals; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D006339:Heart Rate / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000494:pharmacology / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic / Q000502:physiology*; D014981:Xenopus
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins