Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle

Abstract

Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (a(i)Na) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure a(i)Na in guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of a(i)Na. Small increases in a(i)Na were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated a(i)Na by over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, a(i)Na and V(m) returned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+ extrusion. The effects of stimulation on a(i)Na and tension were compared with those of ouabain. The comparison suggests that rapid stimulation could produce increased contraction strength as the result of a substantial gain in intracellular calcium via a Na-Ca exchange mechanism, but that this is only one of several factors determining the force-frequency relationship.