POTASSIUM CURRENTS IN HUMAN FRESHLY ISOLATED BRONCHIAL SMOOTH-MUSCLE CELLS

被引:34
作者
SNETKOV, VA
HIRST, SJ
TWORT, CHC
WARD, JPT
机构
[1] Respiratory Research Laboratories, UMDS Smooth Muscle Group, Department of Allergy and Respiratory Medicine, UMDS, London
基金
英国惠康基金;
关键词
LARGE CONDUCTANCE POTASSIUM CHANNELS; DELAYED RECTIFIER CURRENT; 4-AMINOPYRIDINE; CHARYBDOTOXIN; IBERIOTOXIN; HUMAN BRONCHIAL SMOOTH MUSCLE;
D O I
10.1111/j.1476-5381.1995.tb15926.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 K+ currents were studied in smooth muscle cells enzymatically dissociated from human bronchi, by use of the patch-clamp technique. 2 In whole-cell recordings a depolarization-induced, 4-aminopyridine (4-AP)-sensitive current was observed in only 26 of 155 cells, and in 20 of these 26 cells its amplitude at a test potential of 0 mV was less than 100 pA. 3 In the majority of cells depolarization to -40 mV or more positive potentials induced a noisy outward current which activated within milliseconds and showed almost no inactivation even during a 5 s depolarizing voltage step. This current was insensitive to 4-AP (up to 5 mM) but was strongly inhibited in the presence of tetraethylammonium (TEA, 1 mM), charybdotoxin (ChTX, 100 nM) or iberiotoxin (IbTX, 50 nM) in the bath. The same current was also recorded by the nystatin-perforated patch technique. 4 Single channels with a conductance of about 210 pS were recorded in cell-attached patch, inside-out patch, outside-out patch and whole-cell recording configurations. Channel open state probability in inside-out patches was 0.5 at a membrane potential of 4 +/- 14 mV (mean +/- s.d., n = 13) mV even with a free Ca2+ concentration on the cytosolic side of the patch of less than 0.1 nM. Open state probability increased with depolarization and internal Ca2+ concentration. Single channels could be reversibly blocked by externally applied TEA, ChTX and IbTX. 5 In current-clamp recordings with 100 nM free Ca2+ in the intracellular solution both TEA and ChTX caused substantial concentration-dependent depolarization. 6 These results suggest that in human bronchial smooth muscle cells, in marked contrast to other species, the majority of the outward current induced by depolarization is not due to a delayed rectifier, but to the activity of a large conductance, ChTX-sensitive K+ channel. The Ca2+- and voltage-dependency of this channel may well allow a sufficiently high open state probability for it to play a part in the regulation of the resting membrane potential.
引用
收藏
页码:1117 / 1125
页数:9
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