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

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Abstract
Background Cellular electrophysiological alterations may contribute to arrhythmogenesis in cardiac hypertrophy. An If-like current occurs in left ventricular myocytes (LVMs) isolated from the hypertrophied heart of old spontaneously hypertensive rats (SHR). Factors that influence If 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 If-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 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 If density. In both old WKY and old SHR, 0.1 μmol/L (−)-isoproterenol increased If amplitude by shifting its activation curve toward more positive potentials. Conclusions In LVMs from both WKY and SHR, the occurrence of If increases with aging. Density appears linearly related to the severity of cardiac hypertrophy and increases with β-adrenoceptor stimulation, which suggests that If may contribute to an increased propensity of the hypertrophied heart for arrhythmias.