Effects of strophanthidin on the force-frequency relationship in dog ventricular working and conducting tissues

Effects of strophanthidin on force-frequency relationship were studied in dog working ventricular myocardium (VM) and Purkinje fibers (PF). In VM, both strophanthidin (0.3-1 x 10(-6) M) and driving rate increase within physiological range of 1 to 2 Hz potentiated the force of contraction. In PF, the following different responses were observed. 1. The contractile force decreased as the driving rate increased within the same range (negative staircase). 2. The positive inotropic effect of strophanthidin first increased and then declined. During the rising phase of strophanthidin inotropy, the staircase was still negative. The staircase became positive as strophanthidin inotropy declined. 3. Strophanthidin also potentiated the contractile force of extrasystolic and post-extrasystolic beats as revealed by the Johnson's two-state experiments. 4. The inotropic effects of strophanthidin were mimicked by high [Ca2+] (8.1-12.1 mM) and reversed by Ca channel blockers. Effects of Ca2+ overloading are discussed and a quantitative difference in regulation of cytosolic Ca2+ between VM and PF is suggested.