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 distribution of potassium and calcium currents contribute to the different regional changes in action potential duration in isoprenaline-induced hypertrophy in rats.
METHODS: Hypertrophy was elicited in rats by seven daily injections of isoprenaline. Left ventricular myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial tissue. Membrane 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 in the calcium-independent transient outward current (Ito1) density in hypertrophy were different in the three regions (P < 0.05, ANOVA). Ito1 was reduced 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 not 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 altered in hypertrophy. Calcium current (ICa) density was similar in the three regions studied in both control and hypertrophied hearts. ICa was reduced in hypertrophy (P < 0.05, ANOVA).
CONCLUSION: The normal regional differences in Ito1 are reduced, in steady-state background current are altered and in ICa are unchanged in catecholamine-induced hypertrophy in the rat left ventricle. These data may in part explain the reduction in the normal regional differences in APD observed in hypertrophy.