ACTIVATION OF CA2-SENSITIVE CL- CURRENT BY REVERSE MODE NA+()CA2+ EXCHANGE IN RABBIT VENTRICULAR MYOCYTES/

We investigated how Ca2+-sensitive transient outward current, I-to(Ca) , is activated in rabbit ventricular myocytes in the presence of intra cellular Na+ (Na-i(+)) using the whole-cell patch-clamp technique at 3 6 degrees C. In cells dialysed with Na+-free solutions, the applicatio n of nicardipine (5 mu M) to block L-type Ca2+ current (I-Ca) complete ly inhibited I-to(Ca). In cells dialysed with a [Na+](i)greater than o r equal to 5 mM, however, I-to(Ca) could be observed after blockade of I-Ca, indicating the activity of an I-Ca-independently component. The amplitude of I-Ca-independent I-to(Ca) increased with voltage in a [N a+](i)-dependent manner. The block of Ca2+ release from the sarcoplasm ic reticulum by caffeine, ryanodine or thapsigargin blocked I-Ca-indep endent I-to(Ca). In Ca2+-free bath solution I-to(Ca) was completely ab olished. The application of 2 mM Ni2+ or the newly synthesized compoun d KBR7943, a selective blocker of the reverse mode of Na+/Ca2+ exchang e. or perfusion with pipette solution containing XIP (10 mu M), a sele ctive blocker of the exchanger, blocked I-Ca-independent I-to(Ca). Fro m these results we conclude that, in the presence of Na-i(+). I-to(Cu) can be activated via Ca2+-induced Ca2+ release triggered by Na+/Ca2exchange operating in the reverse mode after blockade of I-Ca.