Channels involved in transient currents unmasked by removal of extracellular calcium in cardiac cells

In cardiac cells that lack macroscopic transient outward K+ currents (I-to), the removal of extracellular Ca2+ can unmask "I-to-like" currents. With the use of pig ventricular myocytes and the whole cell patch-clamp technique, we examined the possibility that cation efflux via L-type Ca2+ channels underlies these currents. Removal of extracellular Ca2+ and extracellular Mg2+ induced time-independent currents at all potentials and time-dependent currents at potentials greater than -50 mV. Either K+ or Cs+ could carry the time-dependent currents, with reversal potential of +8 mV with internal K+ and +34 mV with Cs+. Activation and inactivation were voltage dependent [Boltzmann distributions with potential of half-maximal value (V-1/2)= -24 mV and slope = -9 mV for activation; V-1/2 = -58 mV and slope = 13 mV for inactivation]. The time-dependent currents were resistant to 4-aminopyridine and to DIDS but blocked by nifedipine at high concentrations (IC50=2 muM) as well as by verapamil and diltiazem. They could be increased by BAY K-8644 or by isoproterenol. We conclude that the I(to-)like currents are due to monovalent cation flow through L-type Ca2+ channels, which in pig myocytes show low sensitivity to nifedipine.