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

Background Cellular electrophysiological alterations may contribute to arrhythmognesis 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 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 I-f-like current occurred in >90% of LVMs from old SHR and WKY and in approximate to 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 pico-siemens/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 mu mol/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.