Abstract 20035: Purinergic Endothelium Independent Vasodilation: The Role of Protein Kinase C and Two-Pore Domain Potassium Channels
Background: K+ channels family identified as “two-pore K+- channels (K2P)” function as leak K+ efflux. K2P channels have been reported in pulmonary arteries and mesenteric beds. Which intracellular cascades regulate opening of K2P-channels in thoracic aorta? Could the opening of leak-current impact vasodilation?
Methods and results: Patch-clamp technique was used to record ATPγs-elicited currents in freshly dissociated myocytes. ATPγs elicited bi-phasic response. First ATPγs stimulated burst of Cl-current spikes coupled to Ca2+ oscillations. Then, ATPγs increased amplitude of outward net K+-current. This current was resistive to K+ channels blockers (TEA, 4AP, charibdotoxin, apamin, and glibenclamide). Tested purinergic agonists (ATP, UTP) — except for ADP — activated, delayed K+-current indicating that at least P2Y11 receptor stimulates delayed K+-current. ATPγs increased amplitude of K+ blockers resistive current in 8BrcAMP pretreated cells. PKC agonist (4α-phorbol-12,13-didecanoate) increased amplitude of K+ blockers resistive current. ATPγs added cumulatively to PKC agonist did not further increase the amplitude of the outward net current. ATPγs-elicited K+-current amplitude decreased in staurosporine and G6850 pretreated cells. Acid pH (pH=6) inhibited when basic pH (pH=8) stimulated amplitude of ATPγs-elicited K+-current. ATPγs produced a vasodilation in endothelium-denuded thoracic aorta rings, contracted by the K+-channels blockers and pre-treated by carbenoxolone. PKC agonist mimicked ATPγs-elicited vasodilation.
Conclusions: Our results demonstrate that ATPγs opens K2P-channels via activation of PKC and dilates pre-stretched thoracic aorta rings. Taken together, our data provides new cellular mechanism of vasoregulation in conduit arteries.
- © 2010 by American Heart Association, Inc.