Extracellular proton depression of peak and late Na+ current in the canine left ventricle

Abstract

Cardiac ischemia reduces excitability in ventricular tissue. Acidosis (one component of ischemia) affects a number of ion currents. We examined the effects of extracellular acidosis (pH 6.6) on peak and late Na+ current ( INa) in canine ventricular cells. Epicardial and endocardial myocytes were isolated, and patch-clamp techniques were used to record INa. Action potential recordings from left ventricular wedges exposed to acidic Tyrode solution showed a widening of the QRS complex, indicating slowing of transmural conduction. In myocytes, exposure to acidic conditions resulted in a 17.3 ± 0.9% reduction in upstroke velocity. Analysis of fast INa showed that current density was similar in epicardial and endocardial cells at normal pH (68.1 ± 7.0 vs. 63.2 ± 7.1 pA/pF, respectively). Extracellular acidosis reduced the fast INa magnitude by 22.7% in epicardial cells and 23.1% in endocardial cells. In addition, a significant slowing of the decay (time constant) of fast INa was observed at pH 6.6. Acidosis did not affect steady-state inactivation of INa or recovery from inactivation. Analysis of late INa during a 500-ms pulse showed that the acidosis significantly reduced late INa at 250 and 500 ms into the pulse. Using action potential clamp techniques, application of an epicardial waveform resulted in a larger late INa compared with when an endocardial waveform was applied to the same cell. Acidosis caused a greater decrease in late INa when an epicardial waveform was applied. These results suggest acidosis reduces both peak and late INa in both cell types and contributes to the depression in cardiac excitability observed under ischemic conditions.