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).


CONCLUSIONS
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.
Bryant
S M
SM
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, UK. Simon.Bryant@cardiov.ox.ac.uk
Shipsey
S J
SJ
Hart
G
G
D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D002316:Cardiotonic Agents; D006321:Heart / Q000503:physiopathology*; D017136:Ion Transport; D007545:Isoproterenol; D008297:Male; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium