Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes

Victor A. Maltsev, Hani N. Sabbah, Robert S.D. Higgins, Norman Silverman, Michael Lesch, Albertas I. Undrovinas

Research output: Contribution to journalArticle

Abstract

Background-Alterations in K+ channel expression and gating are thought to be the major cause of action potential remodeling in heart failure (HF). We previously reported the existence of a late Na+ current (I(NaL)) in cardiomyocytes of dogs with chronic HF, which suggested the importance of the Na+ channel in this remodeling process. The present study examined whether this I(NaL) exists in cardiomyocytes isolated from normal and failing human hearts. Methods and Results-A whole-cell patch-clamp technique was used to measure ion currents in cardiomyocytes isolated from the left ventricle of explanted hearts from 10 patients with end-stage HF and from 3 normal hearts. We found I(NaL) was activated at a membrane potential of -60 mV with maximum density (0.34±0105 pA/pF) at -30 mV in cardiomyocytes of both normal and failing hearts. The steady-state availability was sigmoidal, with an averaged midpoint potential of -94±2 mV and a slope factor of 6.9±0.1 mv. The current was reversibly blocked by the Na+ channel blockers tetrodotoxin (IC50= 1.5 μmol/L) and saxitoxin (IC50=98 nmol/L) in a dose-dependent manner. Both inactivation and reactivation of IN(NaL) had an ultraslow time course (τ≃0.6 seconds) and were independent of voltage. The amplitude oaf I(NaL) was independent of the peak transient Na+ current. Conclusions- Cardiomyocytes isolated from normal and explanted failing human hearts express I(NaL) characterized by an ultraslow voltage-independent inactivation and reactivation.

Original languageEnglish (US)
Pages (from-to)2545-2552
Number of pages8
JournalCirculation
Volume98
Issue number23
DOIs
StatePublished - Dec 8 1998
Externally publishedYes

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Keywords

  • Action potentials
  • Heart failure
  • Myocytes
  • Saxitoxin
  • Tetrodotoxin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Maltsev, V. A., Sabbah, H. N., Higgins, R. S. D., Silverman, N., Lesch, M., & Undrovinas, A. I. (1998). Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation, 98(23), 2545-2552. https://doi.org/10.1161/01.CIR.98.23.2545