Contribution of Ca2+-influx to generation of the transient inward current in guinea-pig ventricular muscles.

Contribution of Ca2+-influx via the slow channel to generation of the transient inward current in guinea-pig ventricular muscles was studied using a single sucrose gap voltage clamp technique. The transient inward current (TI) was induced from superfusion of the preparations with the low-K+ (0 mM), high-Ca2+ (3.6 mM) solution. Application of 2 mM-CO2+ quickly and reversibly suppressed the TI amplitude to 25% of the control and delayed its peak timing to 153% during 10-20 min. Inhibition developed as quickly as Co2+ suppressed the slow inward current (Is), and its recovery took place without apparent time lag behind its effect on Is. The block of both TI and Is by Co2+ was antagonized by raising external Ca2+ to 7.2 mM. Removal of external Ca2+ caused a prompt suppression of both Is and TI. Application of 2 or 5 mM-procaine HCl produced a complete abolition of TI with a mild depression of Is. While 1 mM-caffeic caused a suppression of TI after a transient augmentation, 10 mM-caffeine completely eliminated it without abolishing Is. These results indicate that the Ca2+-influx through the slow channel acts not only to load the cell with those ions, but also to influence somehow the Ca2+-release from the stores under the Ca2+-overloaded conditions.