Yx. Wang et al., MODULATION OF MAXI-K-DEPENDENT CA2+ CHANNELS AND METHACHOLINE IN SINGLE AIRWAY MYOCYTES( CHANNELS BY VOLTAGE), American journal of physiology. Cell physiology, 41(4), 1997, pp. 1151-1159
The role of Ca2+ influx through voltage-dependent Ca2+ channels and th
e inhibitory effects of methacholine on large-conductance Ca2+-activat
ed K+ (K-Ca) channels (maxi-K+ channels) were studied in voltage-clamp
ed (nystatin), fura 2-loaded airway smooth muscle cells. Spontaneous t
ransient outward currents (STOCs) were strongly coupled to voltage-dep
endent Ca2+ channel activity; activity was suppressed by nisoldipine a
nd 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 dec
reased the mean outward current. Whole cell current inhibition was obs
erved in the presence of 4-aminopyridine but not in the presence of ch
arybdotoxin. 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 c
onclude that STOCs are activated by influx of Ca2+ through plasmalemma
l 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.