Role of intracellular Na+ activity in the negative inotropy of strophanthidin in cardiac Purkinje fibers.

The relation between intracellular sodium activity (aNai) and different phases of strophanthidin inotropy was studied in sheep cardiac Purkinje fibers superfused in vitro. Strophanthidin (1 microM) progressively increases aNai whereas increases and then decreases contractile force, induces contracture ('mechanical toxicity') and arrhythmias ('electrical toxicity'). Contractile force begins to decrease at approximately 11 mM aNai. Force and aNai show a positive correlation during the increasing and a negative correlation during the decreasing phase of strophanthidin inotropy. In high [K]o (8, 12 and 16 mM), strophanthidin increases aNai and force to a smaller peak and fails to induce toxicity. In high [Na]o (+18.5%), strophanthidin increases aNai and force to a larger peak and induces electrical toxicity below and mechanical toxicity above a higher aNai value (approximately 15 mM). In higher [K]o, high [Na]o restores the ability of strophanthidin to induce mechanical toxicity. Thus, mechanical toxicity begins when aNai increases past a critical value and the continuing aNai increase correlates with decrease in contractile force and contracture. The critical value of aNai is modified by Ca load related to changes in membrane potential or to Na electrochemical gradient.