Selective activation of adrenoceptors potentiates I current in pulmonary vein cardiomyocytes through the protein kinase A and C signaling pathways.

Delayed rectifier K current (I) is a key contributor to repolarization of action potentials. This study investigated the mechanisms underlying the adrenoceptor-induced potentiation of I in pulmonary vein cardiomyocytes (PVC). PVC were isolated from guinea pig pulmonary vein. The action potentials and I current were recorded using perforated and conventional whole-cell patch-clamp techniques. The expression of I was examined using immunocytochemistry and Western blotting. KCNQ1, a I pore-forming protein was detected as a signal band approximately 100 kDa in size, and its immunofluorescence signal was found to be mainly localized on the cell membrane. The I current in PVC was markedly enhanced by both β- and β-adrenoceptor stimulation with a negative voltage shift in the current activation, although the potentiation was more effectively induced by β-adrenoceptor stimulation than β-adrenoceptor stimulation. Both β-adrenoceptor-mediated increases in I were attenuated by treatment with the adenylyl cyclase (AC) inhibitor or protein kinase A (PKA) inhibitor. Furthermore, the I current was increased by α-adrenoceptor agonist but attenuated by the protein kinase C (PKC) inhibitor. PVC exhibited action potentials in normal Tyrode solution which was slightly reduced by HMR-1556 a selective I blocker. However, HMR-1556 markedly reduced the β-adrenoceptor-potentiated firing rate. The stimulatory effects of β- and α-adrenoceptor on I in PVC are mediated via the PKA and PKC signal pathways. HMR-1556 effectively reduced the firing rate under β-adrenoceptor activation, suggesting that the functional role of I might increase during sympathetic excitation under in vivo conditions.