M. Gold, I-Gary R. Strichartz
May 1, 1991
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Journal
Journal of Cardiovascular Pharmacology
Abstract
Summary: Ethylisopropylamiloride (EIPA) is a potent inhibitor of Na+-H+ exchange in many tissues and is frequently used to study cellular regulation of pH, but the electrophysiologic effects of EIPA on cardiac cells have not been studied previously. The use-dependent effects of EIPA on the sodium current (INa) of cultured embryonic chick atrial myocytes were investigated using standard whole-cell patch-clamp techniques. With 150-ms depolarizations from – 140 to 0 mV, applied at 1–3 Hz in the presence of 10 μM EIPA, a decrement INa was observed. This use-dependent reduction equaled 31 × 6% of control INa at steady state during 1-Hz stimulation. Inhibition increased with stimulation rate and with depolarization of the holding potential to –100 mV, but there was no effect of pulse duration on the EIPA-induced inhibition over the range of 20–500 ms. Moreover, repetitive depolarizations to potentials that did not activate macroscopic current but that did yield pronounced channel inactivation did not result in a decrement in INa. The effect of EIPA increased over the concentration range of 1–30 μM so that with 3-Hz stimuli steady-state inhibition increased from 3 × 1 to 85 × 5%. Amiloride, which slows repolarization of the cardiac action potential, was at least 100-fold less potent than EIPA in reducing INa. We conclude that EIPA is an “open-channel” blocker of the cardiac sodium current at concentrations comparable to those of many type I antiarrhythmic agents.