Metabolic inhibition of I(Ca,L) and I(K) differs in feline left ventricular hypertrophy

To determine the intrinsic responsiveness of hypertrophied myocardium, electrophysiological properties of endocardial myocytes enzymatically dissociated from normal and hypertrophied feline left ventricle (LV) were compared during metabolic inhibition by 1 mM CN^-. Chronic pressure overload was induced under surgical anesthesia. A single-pipette, whole cell clamp method was used to record action potential and membrane currents. Before CN^- , action potential duration (APD) values at 90% repolarization (APD₉₀) and at 0 mV (APD(0mV)) were significantly longer in hypertrophied cells. The current density of L-type Ca²⁺ currents (I(Ca,L)) was not significantly different, whereas the time constant of the slow component (τ(s)) of I(Ca,L) inactivation was significantly longer in hypertrophied cells. The current density of delayed rectifier K⁺ current (I(K)) was significantly smaller, the fast component (τ(f)) and τ(s) of I(K) activation were delayed and those of I(K) deactivation were enhanced in hypertrophied cells. During exposure to CN^-, APD shortened significantly more in hypertrophied cells; amplitude of I(Ca,L) decreased, and the τ(f) and τ(s) of I(Ca,L) inactivation shortened only in hypertrophied cells. However, I(K) showed no significant differences in changes in amplitude or kinetics during CN^- exposure between normal and hypertrophied cells. Thus enhanced APD responsiveness to CN^- is an intrinsic property of hypertrophied LV cells and I(Ca,L) appears to be particularly affected by metabolic perturbation in such cells.