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(Circulation. 1996;94:1674-1681.)
© 1996 American Heart Association, Inc.

Articles

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

Elisabetta Cerbai, PhD; Mario Barbieri, PhD; Alessandro Mugelli, MD

the Institute of Pharmacology, University of Ferrara, Italy, and the Department of Pharmacology (A.M.), University of Firenze, Italy.

Correspondence to Alessandro Mugelli, MD, Department of Preclinical and Clinical Pharmacology, University of Firenze, Viale G.B. Morgagni 65, 50134 Firenze, Italy. E-mail mugelli@stat.ds.unifi.it.

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 ß-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 ß-adrenoceptor stimulation, which suggests that I_f may contribute to an increased propensity of the hypertrophied heart for arrhythmias.

Key Words: arrhythmia • electrophysiology • hypertrophy

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