Characterization of a hyperpolarization-activated current in dedifferentiated adult rat ventricular cells in primary culture.

1. The presence of a hyperpolarization-activated pacemaker (I(f)-like current was tested in dedifferentiated adult rat ventricular myocytes up to 12 days in primary culture with the whole-cell patch clamp technique. 2. An I(f)i-like current was found and characterized on freshly isolated and cultured ventricular cells. Both activation and density of the current varied in relation to the stage of dedifferentiation. The current was activated from -92.0 +/- 2.5 and -63 +/- 1.0 mV at the beginning (4-day-cultured cells) and end of the dedifferentiation process (12 days), respectively. Its density measured at 170 mV progressively increased from -2.34 +/- 0.36 to -6.12 +/- 0.64 pA pF-1 between the two farthest stages of cellular remodeling. In freshly isolated cells the current was activated at -108.0 +/- 1.5 mV and its current density measured at -170 mV was -1.97 +/- 0.56 pA pF-1. 3. The current was blocked by extracellular CsCl (3mM) in a voltage-dependent manner. Modification of reversal potentials obtained at various values of [K+]o ( 5.4 or 25 mM) and [Na+]o (140 or 30 mM) suggests that the current was carried by both K+ and Na+ ions. 4. It is concluded that the hyperpolarization-activated inward current, recorded in freshly isolated and in cultured ventricular cells has characteristics similar to those of I(f). In adult rat ventricular cells it is activated in a non-physiological potential range, but can be elicited in a more physiological range when the cells are remodelled through a dedifferentiated way. It is suggested that such a current could be implicated in ventricular arrhythmias developed in pathological events.