β 3 -Adrenergic Regulation of L-Type Ca 2+ Current and Force of Contraction in Human Ventricle

β 3 -Adrenergic receptor (β 3 -AR) is expressed in human atrial and ventricular tissues. Recently, we have demonstrated that it was involved in the activation of L-type Ca 2+ 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 β 3 -AR agonist CGP12177 which also is a β 1 -AR/β 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 β 3 -AR antagonist L-748,337 inhibited the effect of CGP12177. CGP12177 and L748,337 competed selectively on β 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 β 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 β 3 -AR activation has no inotropic effect, while it slightly increases I Ca,L . In contrast to human atrium, the activation of β 3 -ARs in human ventricle is not accompanied by increased activity of phosphodiesterases.