Norepinephrine-induced Inositol 1,4,5-Trisphosphate Formation in Atrial Myocytes is Regulated by Extracellular Calcium, Protein Kinase C, and Calmodulin

Abstract

We investigated whether alteration of extracellular and intracellular Ca²⁺ concentrations, protein kinase C, and calmodulin modulate norepinephrine(NE)-induced inositol 1,4,5-trisphosphate (IP₃) formation in neonatal rat atrial myocytes. NE-induced IP₃ production in atrial myocytes was stimulated by elevation of extracellular Ca²⁺ in a dose-dependent manner. However, TMB-8 (an intracellular calcium antagonist) and A23187 (an intracellular calcium agonist) did not significantly affect NE-induced IP₃ production. PMA (a protein kinase C agonist) significantly decreased and staurosporine (a protein kinase C antagonist) significantly stimulated NE-induced IP₃ production. W7 (a calmodulin antagonist) significantly increased the NE-induced IP₃. In conclusion, elevation of extracellular Ca²⁺ concentrations affects NE-induced IP₃ formation in atrial myocytes. Protein kinase C and calmodulin may control the IP₃ response to NE by a negative feedback mechanism.