Ko. Ryder et al., MEMBRANE CURRENT CHANGES IN LEFT-VENTRICULAR MYOCYTES ISOLATED FROM GUINEA-PIGS AFTER ABDOMINAL AORTIC COARCTATION, Cardiovascular Research, 27(7), 1993, pp. 1278-1287
Objective: The aim was to look for membrane current changes as a basis
for the prolongation of action potential duration in left ventricular
myocytes following abdominal aortic coarctation. Methods: Immature fe
male guinea pigs underwent laparotomy and an aortic coarctation was fa
shioned immediately distal to the renal arteries. After 20 weeks the h
earts were removed and single myocytes were isolated from the left ven
tricles by standard enzymatic techniques. The switch-clamp technique w
as used. Results: Heart weight:body weight ratio was increased by 7% i
n the coarctation group (p<0.01). Systolic left ventricular pressure w
as 59(SEM 4) mm Hg in control and 76(7) mm Hg in coarctation animals (
p<0.05). Cell capacity was increased by 21% in the coarctation group (
p<0.05), and mean resting potential was 4.6 mV more negative in this g
roup (p<0.001). Action potential duration at 90% repolarisation was 31
0(17) ms in the control group (n=22) and 358(13) ms in the coarctation
group (n=34, p<0.05). Peak density of L-type calcium current was -8.6
(0.4) pA.pF-1 in control and -11.1(0.7) pA.pF-1 in coarctation cells (
p<0.01). The regression line for calcium current versus cell capacity
was shifted to higher calcium currents in the coarctation group. The h
alf inactivation potential for this current was shifted by 11.5 mV (p<
0.01). Calcium-activated tail currents were larger and the envelope of
tail currents was prolonged in the coarctation cells. No significant
differences were found in the amplitude of I(K) or of I(Kl). Conclusio
ns: After infrarenal aortic coarctation, action potential duration of
left ventricular myocytes is prolonged. This prolongation may be attri
buted to an increase in calcium current density and a shift of its ina
ctivation variable, together with an increased magnitude and prolonged
time course of sodium-calcium exchange current. These current changes
are potentially arrhythmogenic.