Effects of a combination of acidosis, lactate, and lysophosphatidylcholine on action potentials and ionic currents in guinea pig ventricular myocytes.

Abstract

The aim of this study was to determine the electrophysiological effects of a combination of factors that are of importance during myocardial ischaemia, i.e., acidosis, lactate, and lysophosphatidylcholine, in ventricular myocytes. Intracellular microelectrode techniques were used to record action potential and ionic currents in ventricular myocytes before, during, and after a 30 min exposure to a salt solution that was acidotic (pH 6.8), and contained lactate (10 mM) and lysophosphatidylcholine (5 microM). Single ventricular myocytes were dissociated enzymatically from guinea pig hearts, and perfused with either normal or modified physiological salt solution. Combined acidosis, lactate, and lysophosphatidylcholine resulted in a reduction in the resting membrane potential and maximum rate of depolarisation of phase 0, and flattening of the plateau but prolongation of the action potential duration at 90% repolarisation. Automatic activity was also induced in about one-third of the cells studied. Under voltage-clamp conditions, this combination of factors reduced the peak inward calcium current, on repolarisation after a depolarising step, reduced the steady-state outward current, and reduced the delayed rectifier current, measured as the tail current at the end of a depolarising clamp step. In some cells, a transient inward current was induced by the modified salt solution. It is concluded that the characteristic alterations in action potential characteristics induced by a combination of acidosis, lactate, and lysophosphatidylcholine are likely to result from reductions in the inward Ca current and the background and delayed rectifier K current.