Sodium effects on 4-aminopyridine-sensitive transient outward current in canine ventricular cells.
Tetrodotoxin (TTX) or substitution of external Na+ reduces the 4-aminopyridine-sensitive transient outward current (Ito1) in rat ventricular myocytes. We investigated the outcome of reducing external sodium on the kinetics, gating, and selectivity of Ito1 with a dual-patch electrode technique to record whole cell currents and transmembrane potentials independently of the voltage clamp in canine midmyocardial cells. Steps from -80 to 0 mV produced overlapping inward sodium and outward potassium currents, accompanied by a loss of voltage control associated with activation of INa. Substitution of external Na+ or application of TTX abolished INa, restored voltage control, and reduced Ito1. Inactivation of INa with a 10-ms prestep to -45 mV decreased Ito1 to the same extent as external Na+ substitution. The kinetics, gating, and selectivity of Ito1 recorded after inactivation of INa were unaffected by drastic reductions in external Na+. Our findings suggest that a larger Ito1 in the presence of normal external Na+ is due to 1) transient loss of voltage control and concomitant changes in activation of Ito1 and/or 2) facilitation of an outward current by intracellular Na+. We conclude that reduction of external sodium has no direct effect on the kinetics or gating of Ito1, non does Na+ contribute to current flow through Ito1 channels in canine midmyocardial cells.
Zygmunt
A C
AC
Masonic Medical Research Laboratory, Utica, New York 13501-1787, USA.
Goodrow
R J
RJ
Antzelevitch
C
C
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004553:Electric Conductivity; D005260:Female; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects*
D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D015761:4-Aminopyridine; D011188:Potassium