LACTATE ENHANCES SODIUM-CHANNEL CONDUCTANCE IN ISOLATED GUINEA-PIG VENTRICULAR MYOCYTES

Myocardial hypoxia and ischemia result in the production of lactate. T o study the effect of lactate on the rapid Na+ current (I-Na), we used the whole cell voltage-clamp technique in enzymatically isolated guin ea pig ventricular myocytes. Experiments were conducted at 16 degrees C. Extracellular Na+ concentration ([Na+](o)) was maintained in contro l and test solutions and extracellular pH was 7.4. Lactate (4-10 mM, e ither sodium lactate or lactic acid) augmented I-Na in each of eight e xperiments, increasing the peak Na+ conductance from 75.4 to 84.7 nS ( 13-16% at all test voltages in the linear portion of the conductance c urve). The voltage dependence of steady-state availability and the tim e course of inactivation remained unchanged. The increase in peak Naconductance was concentration dependent, with an apparent dissociation constant of 1.8 mM and Hill coefficient of 1.8. Lactate in the range of 1-10 mM did not significantly reduce the Ca2+ activity of test solu tions. These effects of lactate were still observed in Mg2+-free test solutions and when the buffering capacity of internal solution was rei nforced by increasing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic a cid concentration from 5 to 20 mM. In conclusion, lactate enhances I-N a via a mechanism that does not involve chelation of Ca2+ or Mg2+ or c hanges in intracellular pH. These effects of lactate on the Na+ channe l might alter electrophysiological properties during myocardial ischem ia and could protect the heart from ischemia-induced conduction abnorm alities or, alternatively, could lead to arrhythmias.