Key result
In hypertrophic rat hearts, isoproterenol failed to increase the delayed rectifier potassium current, resulting in significant action potential duration prolongation from 98 ms to 145 ms (P<0.01).
Absolute Event Rate: 145% vs 98%
p-value: p=<0.01
In hypertrophic rat hearts, isoproterenol fails to increase delayed rectifier potassium current due to enhanced phosphodiesterase activity, leading to excessive action potential prolongation.
No immediate clinical implications from rat data; leaves open I(K) as therapeutic target in human hypertrophy.
We investigated the association between sympathetic nerve activity and delayed rectifier potassium current (I(K)) 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), I(K), and L-type calcium current (I(Ca)) were investigated using the whole-cell patch clamp technique. In hypertrophic rats, I(K) was decreased by 28.2%, resulting in significant APD(90) (90% repolarization) prolongation (sham: 55 +/- 3.9, hypertrophy: 98 +/- 11 ms, P = 0.01). Isoproterenol (100 nM)-stimulated I(K) was increased by 54.9% +/- 0.10% in sham-operated rats, but not in hypertrophic rats. On the other hand, isoproterenol increased I(Ca) 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 microM, an adenylyl cyclase stimulator) did not enhance I(K) in hypertrophic rats, but IBMX (100 microM, a nonselective phosphodiesterase inhibitor) enhanced the current (30.2 +/- 0.05%), as much as in sham-operated rats. We concluded that in hypertrophic hearts, I(K) was not increased by isoproterenol because of the enhanced activity of phosphodiesterase, which leads to excessive APD prolongation.
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Sakatani et al. (2006) studied Left ventricular hypertrophy (n=51). Isoproterenol vs. Sham-operated controls / Baseline was evaluated on Action potential duration at 90% repolarization (APD90) (p=<0.01). In hypertrophic rat hearts, isoproterenol failed to increase the delayed rectifier potassium current, resulting in significant action potential duration prolongation from 98 ms to 145 ms (P<0.01).
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