COMPARATIVE INTERACTIONS OF ORGANIC CA++ CHANNEL ANTAGONISTS WITH MYOCARDIAL CA++ AND K+ CHANNELS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (1) , 134-140
Abstract
Dose-dependent inhibition by 3 organic Ca channel antagonists, D-600 [methoxyverapamil], nisoldipine and diltiazem, of the inward Ca current (iCa) and the delayed, outward K current (iK) in single frog atrial cells was examined using a voltage clamp technique. At holding potentials of -60 mV, low concentrations of these antagonists produced considerable inhibition of iCa without significant alterations in iK, suggesting that iK in single frog atrial cells is not a Ca-activated K+ conductance. Higher concentrations of each of these antagonists inhibited iK. The estimated Kd values for inhibition for iCa and iK, respectively, were 3.7 .times. 10-7 M and 8.2 .times. 10-4 M for D-600, 1.6 .times. 10-8 M and 1.6 .times. 10-5 M for nisoldipine and 4.4 .times. 10-6 M and 3.3 .times. 10-4 M for diltiazem. Under these experimental conditions, D-600 and nisoldipine interact more selectively with myocardial Ca2+ channels than K+ channels compared to diltiazem, which is less selective. The inhibition of IK by each of these antagonists exhibited an apparent voltage dependence; block was enhanced at more negative membrane potentials and relieved at more positive membrane potentials. This voltage-dependent block of IK is, therefore, opposite to the voltage-dependent inhibition of iCa produced by these compounds, where block of iCa is accentuated at positive membrane potentials.