In the heart, Na-Ca2 exchange (NCX) is the major Ca2 extrusion mechanism. NCX has been considered as a relaxation mechanism, as it reduces global [Ca2]i raised during activation. However, if NCX locates in the close proximity to the ryanodine receptor, then NCX would curtail Ca2 before its diffusion to global Ca2i. This will result in a global [Ca2]i decrease especially during its ascending phase rather than descending phase. Therefore, NCX would decrease the myocardial contractility rather than inducing relaxation in the heart. This possibility was examined in this study by comparing NCX-induced extrusion of Ca2 after its release from SR in the presence and absence of global Ca2i transient in the isolated single rat ventricular myocytes by using patch-clamp technique in a whole-cell configuration. Global Ca2i transient was controlled by an internal dialysis with different concentrations of BAPTA added in the pipette. During stimulation with a ramp pulse from 100 mV to 100 mV for 200 ms, global Ca2i transient was suppressed only mildly, and completely at 1 mmol/L, and 10 mmol/L BAPTA, respectively. In these situations, ryanodine-sensitive inward NCX current was compared using 100μmol/L ryanodine, Na depletion, 5 mmol/L NiCl2 and 1μmol/L nifedipine. Surprisingly, the result showed that the ryanodine-sensitive inward NCX current was well preserved after 10 mmol/L BAPTA to 91 % of that obtained after 1 mmol/L BAPTA. From this result, it is concluded that most of the NCX-induced Ca2 extrusion occurs before the Ca2 diffuses to global Ca2i in the rat ventricular myocyte.
