Evidence for persistent activation of cardiac slow channels in low-calcium solutions

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Abstract
Action potentials were recorded from frog ventricular strips superfused with Ca-free solutions. Very long action potentials (3-60 s) were induced by chelating residual Ca with 1-5 mM ethyleneglycol-bis(.beta.-aminoethylether)-N,N''-tetraacetic acid (EGTA). Ca influences action potential duration at an intracellular site. In low-Ca solutions isoproterenol was found to lengthen action potentials. The lengthening effect of isoproterenol became progressively greater as [Ca2+] was reduced by elevating [EGTA]. In the presence of 2 mM EGTA, 0.1 .mu.M isoproterenol increased action potential duration from 4.3 .+-. 0.4 to 43 .+-. 14 s. Verapamil produced a > 90% reduction in the duration of very long action potentials (60 s) induced by EGTA, isoproterenol, or both. After rapid or prolonged depolarizations in low-Ca solutions the last 10-30 mV of repolarization may be a manifestation of persistent slow channel activation. Apparently, in low-Ca solutions slow channels can remain activated for many seconds.