Membrane electrical properties of vesicular Na-Ca exchange inhibitors in single atrial myocytes

Na-loading single frog atrial cells produce changes in membrane currents that are similar to the creep currents originally observed in Na-loaded cardiac Purkinje fibers. Exposure to the Na ionophore, monensin, was used to induce creep currents in isolated atrial cells. The sensitivity of myocardial creep currents to three compounds that have been shown to be inhibitors of Na-Ca exchange flux activity in isolated sarcolemmal vesicles was assessed. Dodecylamine, quinacrine, and the amiloride analog, 3',4'-dichlorobenzamil block creep currents at concentrations well below those required to block Na-dependent Ca uptake in sarcolemmal vesicles. The estimated Ki's for inhibition of myocardial creep currents were 3 microM for dodecylamin, 10 micron for quinacrine, and 4 microM for 3',4'-dichlorobenzamil. The sensitivity of creep currents to these compounds is consistent with the hypothesis that creep currents may represent the electrogenic activity of a Na-Ca exchange carrier. In an additional series of experiments, the relative specificity of these compounds was tested by examining their effects on myocardial membrane channels. Both dodecylamine and 3',4'-dichlorobenzamil were found to inhibit myocardial Ca and K currents over the same range of concentrations in which block of exchange activity occurs. These results seriously question the use of these exchange carrier inhibitors as selective experimental probes for defining the role of Na-Ca exchange in various physiological processes.