title: Lactate enhances sodium channel conductance in isolated guinea pig ventricular myocytes.
abstract: Myocardial hypoxia and ischemia result in the production of lactate. To study the effect of lactate on the rapid Na+ current (INa), we used the whole cell voltage-clamp technique in enzymatically isolated guinea pig ventricular myocytes. Experiments were conducted at 16 degrees C. Extracellular Na+ concentration ([Na+]o) was maintained in control and test solutions and extracellular pH was 7.4. Lactate (4-10 mM, either sodium lactate or lactic acid) augmented INa in each of eight experiments, 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 curve). The voltage dependence of steady-state availability and the time course of inactivation remained unchanged. The increase in peak Na+ conductance 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 solutions. These effects of lactate were still observed in Mg(2+)-free test solutions and when the buffering capacity of internal solution was reinforced by increasing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid concentration from 5 to 20 mM. In conclusion, lactate enhances INa via a mechanism that does not involve chelation of Ca2+ or Mg2+ or changes in intracellular pH. These effects of lactate on the Na+ channel might alter electrophysiological properties during myocardial ischemia and could protect the heart from ischemia-induced conduction abnormalities or, alternatively, could lead to arrhythmias.
authors.affiliation: Reingold ECG Center, Northwestern University Medical School, Chicago, Illinois 60611-3008.
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: J A
authors.initials: JA
authors.lastname: Wasserstrom
authors.forename: J E
authors.initials: JE
authors.lastname: Rosenthal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D007773:Lactates; D015222:Sodium Channels; D002118:Calcium