Transient outward current in catecholamine-induced cardiac
hypertrophy in the rat.
Mszros, Jnos, Kathryn O. Ryder, and George Hart.
Department of Cardiovascular Medicine, University of Oxford, John
Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
APStracts 3:0281H, 1996.
We have demonstrated that daily i.p. injection of 5 mg/kg
isoproterenol for 7 days induces a 30% increment in heart weight to
body weight ratio and prolongs the action potential duration (APD) in
male Wistar rats. The underlying mechanism of the prolonged APD was
investigated in this model of hypertrophy by measuring the transient
outward potassium current (Ito) in left ventricular myocytes of the
rat using whole cell voltage clamp techniques. Cell membrane
capacitance was increased by 39% (control, 122 3 pF, mean S.E.M., n =
23; hypertrophy, 171 5 pF, n = 20, p<0.001). Ito was evoked in Na
-free solutions containing 0.9 mM Ca2+ and 2 mM Co2+, by step
depolarizations from a holding potential of -80 mV. The amplitude of
the 4-aminopyridine-sensitive Ito (at 70 mV) was reduced by 28% in
hypertrophy (control, 3.2 0.3 nA, n = 23; hypertrophy, 2.3 0.4 nA, n
= 20, p<0.05). When normalized for cell capacitance the reduction was
much larger (control, 26.4 2.5 pA/pF; hypertrophy, 13.1 1.8 pA/pF,
p<0.001). The voltage dependence of Ito was similar in both cell
types. No change was observed in the steady-state activation and
inactivation kinetics in the two groups, nor was there any change in
the time-dependence of inactivation. The recovery from inactivation
of Ito when fitted with a monoexponential function, was not changed
significantly in hypertrophy (control t = 8.2 0.4 ms, n = 13;
hypertrophy, t = 8.3 0.3 ms, n = 12). These results show that Ito
density is decreased in catecholamine-induced cardiac hypertrophy,
but current kinetics are not affected. The reduced Ito density may
underlie the prolongation of action potential duration seen in this
model of hypertrophy.
Received 17 January 1996; accepted in final form 28 May 1996.
APS Manuscript Number H22-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996