β3-Adrenergic Regulation of L-Type Ca2+ Current and Force of Contraction in Human Ventricle

beta(3)-Adrenergic receptor (beta(3)-AR) is expressed in human atrial and ventricular tissues. Recently, we have demonstrated that it was involved in the activation of L-type Ca2+ current (I (Ca,L)) in human atrial myocytes and the force of contraction of human atrial trabeculae. In the present study, we examined the effect of beta(3)-AR agonist CGP12177 which also is a beta(1)-AR/beta(2)-AR antagonist on I (Ca,L) in human ventricular myocytes (HVMs) and the force of contraction of human ventricular trabeculae. CGP12177 stimulated I (Ca,L) in HVMs with high potency but much lower efficacy than isoprenaline. The beta(3)-AR antagonist L-748,337 inhibited the effect of CGP12177. CGP12177 and L748,337 competed selectively on beta(3)-ARs because L748,337 had no effect on isoprenaline-induced stimulation of I (Ca,L), while CGP12177 completely blocked the effect of isoprenaline. The activation of beta(3)-ARs by CGP12177 does not involve the activation of G(i) proteins because CGP12177 had no effect on forskolin-induced stimulation of I (Ca,L). CGP12177 had no effect on the force of contraction of human ventricular trabeculae. L-NMMA, an inhibitor of NO synthase, and IBMX, a nonselective inhibitor of phosphodiesterases, did not potentiate the effect of CGP12177 either on contraction of human ventricular trabeculae or on I (Ca,L) in HVMs. We conclude that in human ventricles beta(3)-AR activation has no inotropic effect, while it slightly increases I (Ca,L). In contrast to human atrium, the activation of beta(3)-ARs in human ventricle is not accompanied by increased activity of phosphodiesterases.