| Background Hypertrophic growth of the heart is an adaptive response that developsin response to pressure or volume overload. Hypertrophy accompanies many forms ofheart disease including ischemic disease, hypertension, heart failure, valular diseaseand arrhythmia. Hypertrophy is it independent predictor of cardiovascular morbidityand mortality. The most consistent electrophysiological change in myocardialhypertrophy in human being and mammals is prolongation of action potentialthought to be attributable in part to a reduction in the density of calcium-independenttransient outward potassium current (Ito). So the relationship between Ito andhypertrophy is examined necessarily.Objectives The purpose of this study is to investigate the relations betweenreduction of Ito and myocardial hypertrophy and explore its mechanism.Methods Treatment of cultured neonatal rat ventricular myocytes with 4-AP, ablocker of cardiac Ito, induced hypertrophy as indicated by measurements of the cellmembrane capacitance and 3H-Leucine up-take. At the same time, amplitude of Itoand APD were also measured.Results After cultured neonatal rat ventricular myocytes were treated with 4-AP,the amplitude of Ito (pA)was reduced by about 54% (145.1 8.3 pA,n=6 vs67.3 6.2pA,n=4,P<0.05). APD50(ms) (50% repolarization ) was prolongedsignificantly ( 70.7 6.8ms,n=5vs212.5 14.7ms,n=4,P<0.05 ). The membranecapacitance(pF) and the uptake of 3H-Leu were increased by about 42%(P<0.05) and31%(P<0.05). The hypertrophy was prevented by blocking Ca2+entry with Verapamiland blocking calcineurin with Cyclosporine A.Conclusions Reduction of Ito plays an important role in hypertrophy by theincrement of intracellular Ca2+ and activity of calcineurin reaction pathway.
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