Cantharidin increases force of contraction and protein phosphorylation in the isolated human atrium

Abstract

AbstractCantharidin, an inhibitor of protein phosphatases 1 and 2A (PP1, PP2A), is known to increase force of contraction and to shorten time of relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human atrial preparations (HAP). During bypass-surgery trabeculae carneae from human right atrium were obtained. These trabeculae were mounted in organ baths and electrically stimulated (1 Hz). For comparison, we studied isolated electrically stimulated left atrial preparations (LA) and isolated spontaneously beating right atrial preparations (RA) from wild type mice. We noted a concentration-dependent positive inotropic effect of cantharidin, cumulatively applied, starting at 10 µM to 30 µM that reached a plateau at 300 µM in HAP, LA and RA. This positive inotropic effect was accompanied by a shortening of time of relaxation in HAP. Notably, cantharidin did not alter the beating rate in RA. Moreover, cantharidin (100 µM) increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin I in HAP that could account for the faster relaxation, that we had measured. The present data suggest a functional role for PP1 and/or PP2A in human atrial contractility.