Background:, Dopamine is reported to be a coronary vasodilator; however. the exact mechanism of dopamine action in the coronary circulation remains unclear. In this study, we hypothesized that dopamine-induced activation of coronary ATP-sensitive potassium (K-ATp) channels may be associated with coronary vasodilation. We therefore investigated the direct effects of dopamine on coronary K-ATP-channel activity.
Methods: We used patch-clamp configurations to investigate the effects of dopamine on coronary K-ATP-channel activity.
Results: Application of dopamine (10(-9) to 10(-5) M) to the bath solution during cell-attached recordings induced a concentration-dependent increase in K-ATP-channel activity. In contrast, dopamine failed to activate K-ATP channels in inside-out patches. Dopamine-induced coronary K-ATP-channel currents in cell-attached patches were inhibited by pretreatment with the selective D-1-like antagonist, Sch-23390, but they were not influenced by the selective D-2-like antagonist, domperidone, or the beta-adrenergic receptor antagonist, propranolol. The selective D-1-like agonist, SKF-38393, and the adenylyl cyclase activator, forskolin, mimicked the dopamine effects on coronary K-ATP channels. Furthermore, pretreatment with an inhibitor of protein kinase A, Rp-cAMPS, abolished the dopamine-induced K-ATP-channel activation.
Conclusions: This study demonstrates that dopamine activates coronary K-ATP channels via signal transduction involving the D-1-like dopaminergic receptor-protein kinase A-signaling pathway.