Sodium effects on 4-aminopyridine-sensitive transient outward
current in canine ventricular cells.
Zygmunt, Andrew C., Robert J. Goodrow, Charles Antzelevitch.
Masonic Medical Research Laboratory, Utica, NY
APStracts 3:0339H, 1996.
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,
using 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 Na and outward K 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, nor does Na+ contribute to current flow through Ito1
channels in canine midmyocardial cells.
Received 8 April 1996; accepted in final form 25 July 1996.
APS Manuscript Number H311-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996