Effect of strophanthidin on intracellular Na ion activity and twitch tension of constantly driven canine cardiac Purkinje fibers

Abstract

Intracellular Na ion activity (aiNa) and twitch tension (T) of constantly driven (1 Hz) canine cardiac Purkinje fibers were measured simultaneously and continuously with neutral carrier Na+-selective microelectrodes and a force transducer. The aiNa of 8.9 +/- 1.4 mM (mean +/- SD, n = 52) was obtained in the driven fibers perfused with normal Tyrode solution. Temporary interruption of stimulation showed that aiNa of the driven fibers was approximately 1.5 mM greater than that of quiescent fibers. The constantly driven fibers were exposed to strophanthidin of 10(-8), 5 X 10(-8), 10(-7), 5 X 10(-7), and 10(-6) M for 5 min. No detectable changes in aiNa and T were observed in the fibers exposed to 10(-8) M strophanthidin, and the threshold concentration of the strophanthidin effect appeared to be approximately 5 X 10(-8) M. With concentrations greater than 5 X 10(-8) M, strophanthidin produced dose-dependent increases in aiNa and T. An increase in aiNa always accompanied an increase in T and after strophanthidin exposure both aiNa and T recovered completely. During onset and recovery periods of the strophanthidin effect the time course of change in aiNa was similar to that of change in T. A plot of T vs. aiNa during the onset and recovery periods showed a linear relationship between T and aiNa. These results indicate strongly that the positive inotropic effect of strophanthidin is closely associated with the increase in aiNa. Raising [K+]0 from 5.4 to 10.8 mM produced decreases in aiNa and T, and restoration of [K+]0 resulted in recoveries of aiNa and T. During the changes of [K+]0 the time course of change in aiNa was similar to that of the change in T. A steady-state sarcoplasmic Ca ion activity (aiCa) of 112 +/- 31 nM (mean +/- SD, n = 17) was obtained in the driven fibers with the use of neutral carrier Ca2+-selective microelectrodes. Temporary interruption produced 10-30% decreases in aiCa. No detectable changes in aiCa were observed in the fibers exposed to strophanthidin of 10(-7) M or less; 5 X 10(-7) and 10(-6) M strophanthidin produced 1.3-1.6 and 2-3-fold increases in aiCa, respectively. This result is consistent with the hypothesis that an increase in aiNa produces an increase in aiCa, which enhances Ca accumulation in the intracellular stores.