Action potential prolongation and potassium currents in left-ventricular myocytes isolated from hypertrophied rabbit hearts

Abstract

We have studied the action potential characteristics and potassium currents in single left ventricular myocytes isolated from control and hypertrophied rabbit hearts. Left-ventricular hypertrophy (LVH) was induced following perinephritis-induced hypertension. Control animals underwent a sham operation. Animals were killed at 10 weeks post-operation. Left-ventricular myocytes were isolated by an enzyme dissociation technique. Action potential duration (APD) at 50 and 90% repolarisation was prolonged in myocytes obtained from hypertrophied compared to control hearts over the range of stimulation frequencies (0.1-1.5 Hz). This prolongation in APD was more pronounced in epicardial compared to endocardial myocytes. Steady-state ionic current, measured at the end of voltage clamp steps of 3-s duration, stepping at intervals of 10 mV, from a holding potential of -40 mV, was similar in control and hypertrophied myocytes. However, when normalised for capacitative cell surface area, steady-state current was significantly smaller in hypertrophied myocytes over the voltage range -40 to -60 mV and at potentials greater than +10 mV. Inward rectifier potassium current (IKl), identified as the barium chloride (0.1 mM)-sensitive current, contributed to the steady state current at negative potentials. Normalised IKl was significantly smaller in hypertrophied compared to control myocytes at potentials negative to -60 mV. Peak transient outward potassium current (Ito) density was reduced in hypertrophied compared to control myocytes at 0 and +10 mV, from a holding potential -80 mV (12.9 +/- 2.3 v 24.9 +/- 3.9 microA cm2, at +10 mV, P < 0.05). Steady-state inactivation of Ito was similar in control and hypertrophied myocytes. In conclusion, LVH induced by perinephritis hypertension in the rabbit is associated with a prolongation in APD. Reductions in IKl, sustained outward current and Ito may contribute to the prolongation in APD.