Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle

Modulation of the regional distribution of the action potential by left ventricular hypertrophy and the role of the L-type Ca2+ current (I-Ca) and transient outward current (I((t)o)) in the action potential duration (APD) were investigated in normal and hypertrophied rat ventricular myocytes from the apex (A), septum (S) and left ventricular free wall (FW) by using whole cell current-and voltage-clamp techniques. Hypertrophy was induced by abdominal aortic constriction. In control cells, the APD measured at 20% repolarization (APD(20)) assumed the shortest values in the A and the longest in the S, whereas FW cells showed intermediate values. Hypertrophy significantly prolonged the APD(20) and increased APD variability within the A and FW regions but did not modify the APD in S cells. Analysis of the APD, I-Ca, and I-to at the instant of 20% repolarization in the same cell showed that in control cells the shortest APD(20) was associated with a prominent I-to in the A and FW, whereas the long APD(20) was identified with a lower I-to in S myocytes. Hypertrophy-induced prolongation of APD(20) was associated with a reduction in the I-to in the A and FW. Significant correlations could be established between the APD(20) and the ''net current,'' defined as the algebraic addition of I-to and I-Ca in the A and FW control groups but not in the control S or hypertrophied cells whatever their origin. Our results indicate that interregional APD heterogeneity is lost while intraregional APD variability is increased in the A and FW during the hypertrophic process. These effects are largely due to a change in the balance between the I((C)a) and I-to, which is a major contributing factor to the heterogeneity of the initial phase of repolarization in the normal rat ventricle.