| Abstrakt: |
Adenosine 5′-triphosphate (ATP) activated two sequential responses in freshly isolated mouse aortic smooth muscle cells. In the first phase, ATP activated Ca2+-dependent K+ or Cl− currents and the second phase was the activation of a delayed outward current with a reversal potential of −75.9±1.4 mV.A high concentration of extracellular K+ (130 mM) shifted the reversal potential of the delayed ATP-elicited current to −3.5±1.3 mV. The known K+-channel blockers, iberiotoxin, charybdotoxin, glibenclamide, apamin, 4-aminopyridine, Ba2+ and tetraethylammonium chloride all failed to inhibit the delayed ATP-elicited K+ current. Removal of ATP did not decrease the amplitude of the ATP-elicited current back to the control values.The simultaneous recording of cytosolic free Ca2+ and membrane currents revealed that the first phase of the ATP-elicited response is associated with an increase in intracellular Ca2+, while the second delayed phase develops after the return of cytosolic free Ca2+ to control levels.ATP did not activate Ca2+-dependent K+ currents, but did elicit Ca2+-independent K+ currents, in cells dialyzed with ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA). The delay of activation of Ca2+-independent currents decreased from 10.5+3.4 to 1.27±0.33 min in the cells dialyzed with 2 mM EGTA.Adenosine alone failed to elicit a Ca2+-independent K+ current but simultaneous application of ATP and adenosine activated the delayed K+ current. Intracellular dialysis of cells with guanosine 5′-O-(2-thiodiphosphate) transformed the Ca2+-independent ATP-elicited response from a sustained to a transient one. A phospholipase C inhibitor, U73122 (1 μM), was shown to abolish the delayed ATP-elicited response.These results indicate that the second phase of the ATP-elicited response was a delayed Ca2+-independent K+ current activated by exogenous ATP. This phase might represent a new vasoregulatory pathway in vascular smooth muscle cells.British Journal of Pharmacology (2006) 147, 45–54. doi:10.1038/sj.bjp.0706432; published online 31 October 2005 [ABSTRACT FROM AUTHOR] |
