Occurrence and Properties of the Hyperpolarization-Activated Current I f in Ventricular Myocytes From Normotensive and Hypertensive Rats During Aging

Abstract

Background Cellular electrophysiological alterations may contribute to arrhythmogenesis in cardiac hypertrophy. An I f -like current occurs in left ventricular myocytes (LVMs) isolated from the hypertrophied heart of old spontaneously hypertensive rats (SHR). Factors that influence I f occurrence during development of cardiac hypertrophy were studied by determining its presence, amplitude, characteristics, and β-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 I f -like current occurred in >90% of LVMs from old SHR and WKY and in ≈15% of LVMs from young rats ( P <.05). Activation curves of I f 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, I f 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 μmol/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 β-adrenoceptor stimulation, which suggests that I f may contribute to an increased propensity of the hypertrophied heart for arrhythmias.