Sympathetic Potentiation of Cyclic ADP-Ribose Formation in Rat Cardiac Myocytes

Abstract

Sympathetic nerve excitation stimulates β-adrenergic receptors on cardiac myocytes by release of noradrenaline, leading to an increase in the contractility. This cardiostimulant effect is mediated by an increase in Ca²⁺ permeability resulted from cyclic AMP-dependent phosphorylation of voltage-gated ion channels (Figure 1). Opening of phosphorylated L-type Ca²⁺ channels and tetrodotoxin-sensitive Na⁺ channels results in a transient intracellular Ca²⁺ concentration increase ([Ca²⁺]_i transient) which is greater than without sympathetic stimulation. The increased [Ca²⁺]_i is further amplified by Ca²⁺-induced Ca²⁺-release (CICR) from the sarcoplasmic reticulum ryanodine receptor Ca²⁺ release channels, leading to strengthened contraction. In CICR in the heart, both cyclic ADP-ribose (cADP-ribose) and Ca²⁺ cooperatively activate type-II ryanodine receptors to release Ca²⁺. However, no information on the concentration of cADP-ribose after β-adrenoceptor stimulation has yet been reported (Figure 2).