Diminished transient outward currents in rat hypertrophied ventricular myocytes.

Abstract

Action potential duration is prolonged in ventricular hypertrophy induced by sustained pressure overload. Since the transient outward current (I(to)) is a major factor for determining action potential duration in rat ventricular cells, we used patch-clamp techniques to compare the characteristics of I(to) in normal and hypertrophied left ventricular cells of the rat. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4 to 6 weeks before study. Age-matched normal rats served as controls. Pressure overload increased the heart weight-to-body weight ratio by 47.7%. I(to) was significantly smaller in hypertrophied cells than in normal cells (20.0 +/- 1.3 versus 31.0 +/- 2.1 pA/pF, respectively, at a test potential of +60 mV; P < .001). There were no differences in the steady-state inactivation, the inactivation time course, and the time course of recovery from inactivation between normal and hypertrophied cells. At the single-channel level, there were no differences in the unitary current amplitude of the single I(to) channel between normal and hypertrophied cells, and the slope conductance was 13.7 picosiemens in normal cells and 13.4 picosiemens in hypertrophied cells. The maximum open-state probability, which was estimated from the ratio of the peak of the ensemble-averaged currents to the single-channel current amplitude, was similar for normal and hypertrophied cells (0.66 +/- 0.03 and 0.69 +/- 0.04, respectively, at a test potential of +40 mV; P = NS). We conclude that diminished I(to) contributes to action potential prolongation in hypertrophied ventricular cells from pressure-overloaded rat hearts. Reduced I(to) channel density may be responsible for the diminished whole-cell I(to).

Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats

“…A large fraction of the increase in APD has been attributed to a decrease in the Ca 2+ -independent transient outward potassium current (I to ) [1]. I to , however, is not uniformly distributed among the left ventricle.…”

Electrical remodeling in a transgenic mouse model of α1B-adrenergic receptor overexpression

“…Increased ␣ 1 -adrenergic receptor stimulation is also thought to contribute to the higher prevalence of arrhythmias (39). One of the consistent features of heart disease, in both human and experimental model systems, is prolongation of action potential duration (APD), which increases the propensity to develop cardiac arrhythmias (4,24,46). Thus it is possible that increased ␣ 1 -adrenergic stimulation would lead to delayed repolarization, which could increase electrical instability and contribute to arrhythmias in heart failure patients.…”

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

“…It has been shown that long-term administration of IGF-I regulates the expression of the K ϩ channel in cultured neonatal rat ventricular myocytes (18). Most studies regarding the electrophysiological alterations associated with cardiac hypertrophy were performed on the pressure-overload model, which has been associated with reduction in I to (6,15,16,53) and no change (6,57) or a decrease in I K (13,14,29,30) and I K1 (5,15,37). Interestingly, Brooksby et al (5) have shown that the electrical remodeling related to cardiac hypertrophy was restricted to a decrease in I K1 current density with no difference in the resting potential level of cardiomyocytes from control and spontaneously hypertensive rats.…”