ACTION-POTENTIAL PROLONGATION AND POTASSIUM CURRENTS IN LEFT-VENTRICULAR MYOCYTES ISOLATED FROM HYPERTROPHIED RABBIT HEARTS

We have studied the action potential characteristics and potassium cur rents in single left ventricular myocytes isolated from control and hy pertrophied rabbit hearts. Left-ventricular hypertrophy (LVH) was indu ced following perinephritis-induced hypertension. Control animals unde rwent a sham operation, Animals were killed at 10 weeks post-operation . Left-ventricular myocytes were isolated by an enzyme dissociation te chnique, Action potential duration (APD) at 50 and 90% repolarisation was prolonged in myocytes obtained from hypertrophied compared to cont rol hearts over the range of stimulation frequencies (0.1-1.5 Hz). Thi s prolongation in APD was more pronounced in epicardial compared to en docardial 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 hypertr ophied myocytes. However, when normalised for capacitative cell surfac e area, steady-state current was significantly smaller in hypertrophie d myocytes over the voltage range -40 to -60 mV and at potentials grea ter than +10 mV. Inward rectifier potassium current (I-Kl), identified as the barium chloride (0.1 mM)-sensitive current, contributed to the steady state current at negative potentials. Normalised I-Kl was sign ificantly smaller in hypertrophied compared to control myocytes at pot entials negative to -60 mV, Peak transient outward potassium current ( I-to) density was reduced in hypertrophied compared to control myocyte s at 0 and +10 mV, from a holding potential -80 mV (12.9+/-2.3 v 24.9/-3.9 mu A cm(2), at +10 mV, P<0.05). Steady-state inactivation of I-t o was similar in control and hypertrophied myocytes, In conclusion, LV H induced by perinephritis hypertension in the rabbit is associated wi th a prolongation in APD. Reductions in I-Kl, sustained outward curren t and I-to may contribute to the prolongation in APD. (C) 1998 Academi c Press Limited.