Muscarinic regulation of membrane ion channels in airway smooth muscle cells.
We have demonstrated that stimulation of airway smooth muscle by muscarinic agonists results in a coordinated modulation of two membrane ion channel proteins. Both channels are modulated in a similar way, although their effects on open-channel probability are opposite. The voltage-dependence of channel activity is shifted to more positive potentials in the case of KCa, and to more negative potentials in the case of the voltage-dependent calcium channels. Similarly, KCa channel dwell-time kinetics are shifted to short open lifetimes, whereas the long open state is favored for the large-amplitude voltage-dependent calcium channel. Although little is known about the molecular coupling of calcium channels, muscarinic inhibition of KCa channels is mediated through a pertussis toxin-sensitive guanine nucleotide binding protein.
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046.
M I
MI
Kotlikoff
H
H
Kume
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M
Tomasic
D000818:Animals; D004095:Dihydropyridines / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D016210:Methacholine Chloride / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D010277:Parasympathomimetics / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism
D004095:Dihydropyridines; D007473:Ion Channels; D010277:Parasympathomimetics; D016210:Methacholine Chloride; C038806:1,4-dihydropyridine; D006160:Guanosine Triphosphate