LATE SODIUM CURRENT INHIBITION IN HUMAN ISOLATED CARDIOMYOCYTES BY R-56865

R 56865, a cytoprotective agent, has been shown to prevent myocardial ischemia and reperfusion injury by blockade of the late sodium current (I-Nal) The effect of R 56865 on I-Nal in isolated human atrial myocy tes was investigated by using the whole-cell patch-clamp technique. I- Nal recorded at the end of a 350-ms test pulse evoked from -100 to +20 mV was significantly increased by the addition of veratrine (100 mu g /ml: quantity of charge corresponding to total I-Nal: 6.1 +/- 1.2 at b aseline vs. 86.9 +/- 15; p < 0.001). Tetrodotoxin (TTX; 1 mu M) fully prevented veratrine-induced increases in I-Nal R 56865 (0.1-10 mu M, n = 14) significantly and reversibly decreased veratrine-induced I-Nal (42.01 +/- 8.6%, n = 6; p < 0.001 at 10 mu M) Moreover, R 56865 reduce d I-Nal without significantly affecting kinetic parameters of inactiva tion [tau 1 = 1.04 +/- 0.1 ms and tau 2 = 119.3 +/- 2.3 ms (base-line) vs. tau 1 = 1.57 +/- 0.5 ms and tau 2 = 134.4 +/- 14 ms in the presen ce of 10 mu M R 56865; NS]. The data indicate that R 56865 is a potent blocker of the late inducible component of sodium current in human ca rdiomyocytes.