Occurrence and properties of the hyperpolarization-activated current If in ventricular myocytes from normotensive and hypertensive rats during aging

Abstract

Background: Cellular electrophysiological alterations may contribute to arrhythmogenesis in cardiac hypertrophy. An L-like current occurs in left ventricular myocytes (LVMs) isolated from the hypertrophied heart of old spontaneously hypertensive rats (SHR). Factors that influence L occurrence during development of cardiac hypertrophy were studied by determining its presence, amplitude, characteristics, and beta-adrenoceptor modulation.

Methods and results: Patch-clamped LVMs from young (2 to 3 months old) or old (18 to 24 months old) normotensive Wistar-Kyoto rats (WKY) and SHR were used. A diastolic depolarization phase was present in old SHR. An If-like current occurred in > 90% of LVMs from old SHR and WKY and in approximately = 15% of LVMs from young rats (P < .05). Activation curves of If were similar in old rats, with the midpoint at -92.9 +/- 2.9 mV in WKY (n = 42) and -88.1 +/- 1.5 mV in SHR (n = 25); maximal specific conductance was 54.4 +/- 1.7 in SHR and 20.1 +/- 0.5 picosiemens/picofarad in WKY (P < .05). In WKY, If amplitude was linearly related to membrane capacitance, an index of cell size (r = .53, P < .001). This relation was absent in SHR, in which a significant positive correlation was found between the heart weight to body weight ratio and I(f) density. In both old WKY and old SHR, 0.1 mumol/L (-)-isoproterenol increased I(f) amplitude by shifting its activation curve toward more positive potentials.

Conclusions: In LVMs from both WKY and SHR, the occurrence of I(f) increases with aging. Density appears linearly related to the severity of cardiac hypertrophy and increases with beta-adrenoceptor stimulation, which suggests that I(f) may contribute to an increased propensity of the hypertrophied heart for arrhythmias.