Effects of forskolin on intracellular sodium activity in resting and stimulated cardiac Purkinje fibers from sheep.

In the present investigation, the effects of forskolin on intracellular sodium activity were studied in quiescent and electrically stimulated cardiac Purkinje fibers from sheep using Na+-sensitive microelectrodes. Also assessed, were the effects of this promoter of cytosolic cAMP production on resting membrane potential, action potential and twitch tension. In the quiescent fibers, forskolin (12 microM) caused intracellular sodium activity to decrease in the face of cellular depolarization. This cellular depolarization was occasionally accompanied by spontaneous firing of action potentials. In the stimulated fibers, forskolin (10 microM) also caused intracellular sodium activity to decrease. Moreover, it caused a marked acceleration of phase 4 pacemaker depolarization, an elevation of the plateau of the action potential and an increase in twitch tension. When the Na+ pump was inhibited by either strophanthidin (1 microM) or by 0 mM extracellular K+, forskolin had no effect on intracellular sodium activity. In summary, the results of the present study indicate that forskolin, presumably by increasing intracellular cAMP, causes the following to occur in cardiac Purkinje fibers from sheep: (a) a decrease in intracellular sodium activity when the Na+ pump is functioning normally; (b) a promotion of membrane depolarization in quiescent fibers; (c) an increase in the steepness of the pacemaker potential in electrically stimulated fibers, and (d) an increase in the force of contraction. Therefore, forskolin will be a useful tool for investigating the role of cAMP in physiological function of cardiac cells.