Effects of concanavalin A on cardiotonic responses to A23187 and isoprenaline.

Effects of the lectin concanavalin A on cardiotonic response to A23187 and isoprenaline were examined in guinea-pig papillary muscles driven at 0.2 Hz. Concanavalin A (Con A) alone did not affect the cardiac action potential and contractility at concentrations up to 3.6 x 10(-4) g/ml. The contraction increased by isoprenaline, beta-adrenoceptor agonist, was not significantly affected by Con A in this concentration range. However, the positive inotropic effect of A23187 (10(-6) M) was markedly inhibited by this lectin. The maximum inhibitory action was observed at 1.8 x 10(-4) g/ml, while below 3.6 x 10(-5) g/ml, Con A failed to inhibit the inotropic effect of A23187. The inhibitory effect of Con A (3.6 x 10(-4) g/ml) was observed only on the late component of biphasic contraction induced by A23187, and then A23187-induced prolongation of the action potential duration at an early repolarization phase (APD 10) also disappeared. Similar inhibitory action was caused by nifedipine (10(-6) M), but in contrast to Con A, nifedipine markedly inhibited the action potential plateau and the contraction by itself. In the presence of Con A, the residual inotropic effect of A23187 on the early component of contraction was blocked by ryanodine (2 x 10(-6) M). The present inhibitory effect of Con A was completely blocked by the pre-treatment with either alpha-methyl-D-mannoside (10 mM) or endoglycosidase F (1 mU/ml). Succinyl Con A (3.6 x 10(-4) g/ml) and wheat germ agglutinin (2.4 x 10(-4) g/ml) did not significantly affect the positive inotropic effect of A23187. In voltage clamp experiments, the slow inward current was markedly augmented by A23187. This augmentation was nearly completely inhibited by Con A. These results suggest that Con A prevents the process of activation of Ca channels by A23187 through the binding of this lectin to specific carbohydrate residues presumably resulting in cross-linking of glycoproteins on membrane surface. Con A-sensitive carbohydrate residue is assumed to be involved in the modulation of Ca channel activation by A23187.