Modulation of maxi-K+ channels by voltage-dependent Ca2+ channels and methacholine in single airway myocytes.
The role of Ca2+ influx through voltage-dependent Ca2+ channels and the inhibitory effects of methacholine on large-conductance Ca2+-activated K+ (K(Ca)) channels (maxi-K+ channels) were studied in voltage-clamped (nystatin), fura 2-loaded airway smooth muscle cells. Spontaneous transient outward currents (STOCs) were strongly coupled to voltage-dependent Ca2+ channel activity; activity was suppressed by nisoldipine and Cd2+ and increased by BAY K 8644 within seconds. Moreover, release of intracellular Ca2+ by caffeine or cyclopiazonic acid only partially suppressed STOCs, and the remainder were almost completely blocked by nisoldipine. Methacholine suppressed STOCs but also significantly decreased the mean outward current. Whole cell current inhibition was observed in the presence of 4-aminopyridine but not in the presence of charybdotoxin. Caffeine inhibited STOCs but macroscopic outward currents were not altered. In the continued presence of caffeine, methacholine abolished the remaining STOCs and decreased the mean K+ current. We conclude that STOCs are activated by influx of Ca2+ through plasmalemmal voltage-dependent Ca2+ channels, as well as by release of Ca2+ from intracellular stores, and muscarinic stimulation depresses the mean K(Ca) current via a pathway independent of the depletion of intracellular Ca2+ stores.
Wang
Y X
YX
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA.
Fleischmann
B K
BK
Kotlikoff
M I
MI
D000818:Animals; D002118:Calcium / Q000172:deficiency; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D006736:Horses; D007425:Intracellular Membranes / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D015220:Calcium Channels; D018721:Muscarinic Agonists; D015221:Potassium Channels; D016210:Methacholine Chloride; D002118:Calcium