Abstract
We investigated the association between sympathetic nerve activity and delayed rectifier potassium current (IK) in hypertrophic rat hearts. Left ventricular hypertrophy was induced by a 50% constriction of suprarenal abdominal aorta for 6 weeks. The effects of isoproterenol on action potential duration (APD), IK, and L-type calcium current (ICa) were investigated using the whole-cell patch clamp technique. In hypertrophic rats, IK was decreased by 28.2%, resulting in significant APD90 (90% repolarization) prolongation (sham: 55 ± 3.9, hypertrophy: 98 ± 11 ms, P = 0.01). Isoproterenol (100 nM)-stimulated IK was increased by 54.9% ± 0.10% in sham-operated rats, but not in hypertrophic rats. On the other hand, isoproterenol increased ICa in both sham-operated (77.7% ± 7.6%) and hypertrophic rats (69.6% ± 9.7%). Consequently, isoproterenol prolonged further APD in hypertrophic rats (98 ± 11 vs. 145 ± 8.6 ms, P < 0.01), but not in sham-operated rats (55 ± 3.9 vs. 61 ± 5.6 ms, n.s.). Forskolin (1 μM, an adenylyl cyclase stimulator) did not enhance IK in hypertrophic rats, but IBMX (100 μM, a nonselective phosphodiesterase inhibitor) enhanced the current (30.2 ± 0.05%), as much as in sham-operated rats. We concluded that in hypertrophic hearts, IK was not increased by isoproterenol because of the enhanced activity of phosphodiesterase, which leads to excessive APD prolongation.
