Effects of components of ischemia on the Kv4.3 current stably expressed in Chinese hamster ovary cells
Effects of components of ischemia on the Kv4.3 current stably expressed in Chinese hamster ovary cells
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DOI:
10.1006/jmcc.2001.1502
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发表时间:
2002-02-01
影响因子:
5
通讯作者:
Campbell, T
中科院分区:
文献类型:
--
作者:
Singarayar, S;Singleton, C;Campbell, T
We investigated the effects of three components of ischemia: external acidosis (pH=6.0), extracellular hyperkalemia ([K+]=20 mmol/l), and resting membrane depolarization to −60 mV, on Kv4.3 current stably expressed in Chinese Hamster Ovary cells. We used single electrode whole cell patch clamp techniques to study changes in the current elicited. External acidosis caused a positive shift in the steady state activation curve from −13.4±2.1 mV to −3.3±1.5 mV (n=8, P=0.004) and the steady state inactivation curve from −56.5±0.4 mV to −46.7±0.5 mV (n=14, P<0.0001). Acidosis also caused an acceleration of recovery from inactivation with the t1/2decreasing from 306 ms (95% CI 287–327 ms) to 194 ms (95% CI 182–207 ms), (n=14, P<0.05). Hyperkalemia did not affect any of these parameters. Combined acidosis and hyperkalemia produced effects similar to those seen with acidosis. Changing the holding potential from −90 mV to −60 mV with test potentials of +5 and +85 mV decreased the peak currents by 34.1% and 32.4% respectively (n=14). However, in the presence of external acidosis the decrease in peak currents induced by changing the holding potential was less marked. In acidotic bath the peak current at −60 mV was reduced by only 13.6% at a test potential of +5 mV and 12.3% at a test potential of +85 mV (n=14). Taken together our data suggest that the membrane depolarization and changes in pH which occur under ischemic conditions would be accompanied by relative preservation of Kv4.3 currents and provide a molecular basis for the observation of preserved epicardial Itoand epicardial action potential duration (APD) shortening in ischemia.