%0 Journal Article
%T 汐1-adrenergic Receptor Attenuates 汕1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes
%J -
%D 2019
%X The rapid delayed rectifier K+ current (Ikr) is critical for repolarization of the cardiac action potential. Previous studies have shown activated 汐1-adrenergic receptor (AR) attenuates 汕1-adrenergic regulation of Ikr while the mechanisms involved are poorly understood. To evalutate how 汐1-adrenergic receptor affect 汕1-adrenergic modulation of Ikr, whole-cell patch-clamp recordings were peformed in isolated guinea-pig ventricular myocytes. Application of xamoterol, a selective 汕1-AR agonist, induced a negative shift in the activation curve and Ikr current reduction by 40.50㊣6.66% at the test pulse of +40 mV. Forskolin and 8-Br-cAMP also resulted in Ikr reduction by 38.17㊣1.50% and 24.65㊣3.37%, respectively. Phenylephrine, a selective 汐1-AR agonist, prevented the activation shift and Ikr current reduction induced by xamoterol and forskolin, but not by 8-Br-cAMP. The effect of xamoterol or forskolin on Ikr was also prevented by pretreatment with PDBu, a protein kinase C (PKC) activator, while the effect of cAMP on Ikr can not, which was similar to pretreatment with phenylephrine. When cells were pretreated with chelerythrine, a specific PKC inhibitor, phenylephrine failed to prevent Ikr reduction induced by xamoterol. Our data suggests that 汐1-adrenergic stimulation attenuates 汕1-adrenergic regulation of Ikr, through PKC-dependent downregulation of adenylyl cyclase/cyclic AMP pathway
%K Adrenergic Receptors
%K Ikr
%K Cross-talk
%K Protein Kinase C
%K Adenylyl Cyclase
%U http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=335&doi=10.11648/j.ijcems.20190502.11