Lactate enhances sodium channel conductance in isolated guinea pig ventricular myocytes

H. Guo, J. A. Wasserstrom, J. E. Rosenthal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Myocardial hypoxia and ischemia result in the production of lactate. To study the effect of lactate on the rapid Na+ current (I(Na)), we used the whole cell voltage-clamp technique in enzymatically isolated guinea pig ventricular myocytes. Experiments were conducted at 16°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 I(Na) 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 Mg2+-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 I(Na) 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.

Original languageEnglish (US)
Pages (from-to)H1565-H1572
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number4 36-4
DOIs
StatePublished - 1994

Keywords

  • dose-response curve
  • electrophysiology
  • heart
  • whole cell patch clamp

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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