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Under the influence of cardiotonic steroids, single ventricular cells exhibit transient depolarization after a train of driven action potentials or, in voltage clamp experiments, transient inward current after a depolarizing clamp pulse. Transient depolarization or transient inward current was abolished by an intracellular injection of ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or by superfusion of 5 mM caffeine. Transient depolarization was elicited even in the control Tyrode's solution by an intracellular injection of CaCl2 or augmented by an injection of adenosine 3',5'-cyclic monophosphoric acid (cAMP). Along with transient depolarization or transient inward current, digitalis intoxication promoted spontaneous oscillatory fluctuations in membrane potential or in membrane current. Their power spectra showed peaks at frequencies ranging from 2 to 7 Hz, which coincided well with the frequency of repetitive transient depolarization or transient inward current. The fluctuations were eliminated by intracellular injections of EGTA and decreased in amplitude by 5 mM caffeine with a shift toward higher frequencies. Depolarization of the membrane caused a shift of the spectrum peak toward higher frequencies. These results suggest that an oscillatory release of Ca from intracellular storage sites is the common basis underlying both the transient events (depolarization or inward current) and the spontaneous miniature fluctuations in membrane potential or current.

circulation research

Transient depolarization and spontaneous voltage fluctuations in isolated single cells from guinea pig ventricles. Calcium-mediated membrane potential fluctuations.