Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy

Objective: To test the hypothesis that changes in the normal regional distr ibution of potassium and calcium currents contribute to the different regio nal changes in action potential duration in isoprenaline-induced hypertroph y in rats. Methods: Hypertrophy was elicited in rats by seven daily injecti ons of isoprenaline. Left ventricular myocytes were isolated from basal sub -endocardial, basal mid-myocardial and apical sub-epicardial tissue. Membra ne currents were measured using the whole-cell patch-clamp technique at 35/-1 degrees C. Results: Cell membrane capacitance was similar in all three groups and was increased by 17% in hypertrophy (P<0.001, t-test). Changes i n the calcium-independent transient outward current (I-to1) density in hype rtrophy were different in the three regions (P<0.05, ANOVA). I-to1 was redu ced in sub-epicardial (control, 23.4+/-2.0 pA pF(-1); hypertrophy, 15.8+/-1 .5 pA pF(-1), P<0.01 ANOVA) and in mid-myocardial myocytes (control, 24.0+/ -2.8 pA pF(-1); hypertrophy, 13.8+/-1.3 pA pF(-1), P<0.01 ANOVA) and was no t significantly altered in sub-endocardial myocytes (control, 8.5+/-0.7 pA pF(-1); hypertrophy, 7.4+/-1.8 pA pF(-1)). Steady-state background current density was reduced in hypertrophy (P<0.05, ANOVA). The regional difference in steady-state background current in control hearts (P<0.05, ANOVA) was a ltered in hypertrophy. Calcium current (I-Ca) density was similar in the th ree regions studied in both control and hypertrophied hearts. I-Ca was redu ced in hypertrophy (P<0.05, ANOVA). Conclusion: The normal regional differe nces in I-to1 are reduced, in steady-state background current are altered a nd in I-Ca are unchanged in catecholamine-induced hypertrophy in the rat le ft ventricle. These data may in part explain the reduction in the normal re gional differences in APD observed in hypertrophy. (C) 1999 Elsevier Scienc e B.V. All rights reserved.