MECHANISM OF RAPID DESENSITIZATION OF MUSCARINIC K+ CURRENT IN ADULT-RAT AND GUINEA-PIG ATRIAL CELLS

被引:42
作者
KIM, DH
机构
[1] Dept. of Physiology and Biophysics, Chicago Medical School, North Chicago, IL
[2] Dept. of Physiology and Biophysics, Chicago Medical School, North Chicago, IL 60064
关键词
MUSCARINIC K+ CHANNEL; DESENSITIZATION; MG2+ -ATP; PHOSPHORYLATION; RATS; GUINEA PIGS; ATRIAL CELLS; PATCH CLAMP;
D O I
10.1161/01.RES.73.1.89
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acetylcholine (ACh) activates the muscarinic K+ current in atrial cells via the inhibitory GTP binding protein. After activation, the whole-cell K+ current decreases rapidly (rapid desensitization) to approximately half of the initial current within almost-equal-to 20 seconds. The mechanism of this rapid desensitization was investigated in adult rat and guinea pig atrial cells. Whole-cell voltage-clamp and patch-clamp techniques were used to study the K+ current. In voltage-clamped whole cells, ACh activated a K+ current that desensitized rapidly during the initial almost-equal-to 20 seconds followed by a slower decrease over several minutes. The rapid K+ current desensitization (a rapid decrease in channel open probability) was also observed at the single-channel level in cell-attached patches and was associated with a progressive shortening of the channel open time and prolongation of the closed time. These changes in channel current and kinetics were abolished by removal of the cytoplasm (by forming inside-out patches) and were partially inhibited by phosphatase inhibitors, suggesting an involvement of cytosolic phosphatase(s) in K+ current desensitization. In inside-out patches with ACh in the pipette and GTP in the bath, the open time of muscarinic K+ channels and channel open probability were increased by 1 mM Mg2+-ATP (but not by the nonhydrolyzable analogue, adenylylimidodiphosphate) and decreased by alkaline phosphatase. These results suggest that the rapid K+ current desensitization in adult rat or guinea pig atrial cells is produced by changes in the gating kinetics of the K+ channel, possibly mediated via membrane-associated protein kinase and cytosolic phosphatase(s).
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页码:89 / 97
页数:9
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