Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes

VA Maltsev, HN Sabbah, RSD Higgins, N Silverman… - Circulation, 1998 - Am Heart Assoc
VA Maltsev, HN Sabbah, RSD Higgins, N Silverman, M Lesch, AI Undrovinas
Circulation, 1998Am Heart Assoc
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 (INaL) 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 INaL exists in cardiomyocytes isolated from normal and failing
human hearts. Methods and Results—A whole-cell patch-clamp technique was used to …
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 (INaL) 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 INaL 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 INaL was activated at a membrane potential of −60 mV with maximum density (0.34±0.05 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 INaL had an ultraslow time course (τ≈0.6 seconds) and were independent of voltage. The amplitude of INaL was independent of the peak transient Na+ current.
Conclusions—Cardiomyocytes isolated from normal and explanted failing human hearts express INaL characterized by an ultraslow voltage-independent inactivation and reactivation.
Am Heart Assoc