Effects of beta-adrenoceptor stimulation on intracellular Ca transients and tension in rat ventricular muscle

Abstract

Effects of beta-adrenoceptor stimulation on intracellular Ca2+ transients and tension were explored in rat ventricular muscles injected with aequorin. Adrenaline (0.05-5.0 microM) and isoproterenol (0.05-1.0 microM) increased the peak of twitch tension and accelerated relaxation. The former effect depended on Ca2+ concentration in Tyrode's solution ([Ca2+]o) and the stage of the experiment. Low concentrations of these drugs added to normal Tyrode's solution containing 2 mM [Ca2+]o did not potentiate twitch tension in the early stage of the experiments. These drugs increased the peak of the aequorin light signal and slightly accelerated the falling phase of the light especially the tail. Effects of dibutyryl-cyclic AMP (DB-cAMP)(0.1-5.0 mM) and 3-isobutyl-1-methylxanthine (IBMX) (0.01-0.5 mM) were qualitatively similar to those of adrenaline and isoproterenol. Isoproterenol applied at the peak of Na-deficient contracture decreased tension without significantly changing the light signal; similar results were obtained in the presence of ryanodine (1 microM). The results were interpreted as follows: The increase of intracellular cAMP induced by beta-adrenoceptor stimulation facilitated Ca2+ uptake by sarcoplasmic reticulum (SR) and decreased Ca2+ sensitivity of contractile elements. Faster relaxation induced by cAMP was considered to be due to the decrease of Ca2+ sensitivity of contractile elements and faster Ca2+ uptake by SR. The slightly faster falling phase of light transient might be due to the faster Ca2+ uptake by SR, which predominates over the slower fall of [Ca2+]i induced by the decreased Ca2+ sensitivity of the contractile element.