Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions.

An inward current characterized by a slow inactivation, was induced when the extracellular Ca2+ concentration was reduced by EGTA. It was suppressed by replacing external Na+ with Tris+ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na+ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 microM for Ca2+ and 60 microM for Mg2+. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa = 7.5 or pCa greater than 8, the single channel I - V relationship was linear and the slope conductance was 70-75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa = 6 than at pCa = 7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around -40 mV (pCa greater than 8, with 5 microM Bay K 8644 in the bath solution), which was decreased with increasing the Ca2+ concentration in the pipette solution. Noise power spectra of patch currents at pCa = 6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca2+ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca2+ might be attributed to a rapid block by Ca2+.