AIMTo study whether the mAchR agonist Carbachol(Cch, nonselective) causes increased contractions and L-type Ca2+ current [L(Ca(L))] in ventricular myocytes and the mechanism of these effects.

METHODSThe effect of Cch on the I(Ca(L)) and Na/Ca exchange current (I(Na/Ca) was studied in patch-clamped ventricular myocytes isolated from rat hearts and superfused with Tyrode's solution (35 degrees C, 1.8 mmol/L [Ca2+]o) and stimulated at 0.2 Hz and 1.0 Hz evoke contractions of single myocyte.

RESULTS(1) An increase of stimulation frequency decreased the contractions of myocytes(negative inotropic effects). (2) 100 micromol/L Cch increased contraction in 6 cells by 28% (delta L0.2 Hz/ delta L1.0 Hz > or = 1.25) at 1.0 Hz stimulus frequency. (3) The mAchR antagonist Atropine prevented the Cch effect. The mAchR agonist McN-A-343 (M1-selective) did not change the contractions in most of the cells. (4) 100 micromol/L Cch had no significant effect on basal I(Ca(L)), but increased the tail current density on repolarization from +10 mV to -40 mV, suggested that Cch increased I(Na/Ca).

CONCLUSIONThe increase of cell contractions by Cch is apparently mediated by M2 mAchR and eventually increased I(Na/Ca). The increase Ca2+ content of the SR is reflected by the greater magnitude of I(Na/Ca). These results provide an explanation for the increased contraction of the rat ventricular myocytes by Cch and without changes in I(Ca(L)).