Purinergic activation of a leak potassium current in freshly dissociated myocytes from mouse thoracic aorta

Exogenous ATP elicits a delayed calcium-independent K+ current on freshly isolated mouse thoracic aorta myocytes. We investigated the receptor, the intracellular pathway and the nature of this current. The patch-clamp technique was used to record ATP-elicited delayed K+ current in freshly dissociated myocytes. ATP-elicited delayed K+ current was not inhibited by a 'cocktail' of K+ channel blockers (4-AP, TEA, apamin, charybdotoxin, glibenclamide). The amplitude of the delayed K+ current decreased after the reduction of extracellular pH from 7.4 to 6.5. These two characteristics suggest that this current could be carried by the TASK subfamily of 'twin-pore potassium channels' (K2P). Purinergic agonists including dATP, but not ADP, activated the delayed K+ current, indicating that P2Y(11) is the likely receptor involved in its activation. The PKC activator phorbol ester 12,13-didecanoate stimulated this current. In addition, the PKC inhibitor Go 6850 partially inhibited it. Real-time quantitative PCR showed that the genes encoding TASK-1 and TASK-2 are expressed. Our results indicate that blocker cocktail-insensitive delayed K+ current in freshly dissociated aortic myocytes is probably carried by the TASK subfamily of twin-pore channels.