Verapamil Diminishes Action Potential Changes During Metabolic Inhibition by Blocking ATP‐Regulated Potassium Currents
作者:
Shinichi Kimura,
Arthur Bassett,
Hongying Xi,
Robert Myerburg,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 71,
issue 1
页码: 87-95
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: patch clamp;ventricular myocytes;cyanide;ischemia
数据来源: OVID
摘要:
Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+(KATP) current in action potential shortening and K+loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATPcurrent in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATPchannel. Membrane potentials and currents were recorded using standard patch-clamp techniques. During 15-minute superfusion with 1 mM CN−, action potential duration measured at 90% repolarization was reduced from 259±12 to 98±15 msec (62% reduction) in the absence of verapamil and from 266±11 to 183±16 msec (31% reduction) in the presence of 2 μM verapamil (p<0.01). In inside-out membrane patches, the KATPcurrent, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 μM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92±0.18 and 1.82±0.21 msec in the absence and presence of 2 μM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1±3.5 to 24.9±2.8 msec (p<0.01) and prolonged the closed time between bursts from 39.4±4.6 to 78.5±5.1 msec (p<0.01). As a result, the open-state probability of the channel was significantly reduced from 0.31±0.04 to 0.03±0.01 (p<0.01). We suggest that these effects of verapamil on the KATPchannel in isolated ventricular myocytes provide, in part, an explanation for its amelioration of electrophysiological disturbances and K+loss during ischemia.
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