| 16258525 |
Serir K, Hayoz S, Fanchaouy M, Beny JL, Bychkov R: A delayed ATP-elicited K+ current in freshly isolated smooth muscle cells from mouse aorta. Br J Pharmacol. 2006 Jan;147(1):45-54.
Adenosine 5'-triphosphate (ATP) activated two sequential responses in freshly isolated mouse aortic smooth muscle cells. In the first phase, ATP activated Ca (2+)-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, Ba (2+) 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 Ca (2+) and membrane currents revealed that the first phase of the ATP-elicited response is associated with an increase in intracellular Ca (2+), while the second delayed phase develops after the return of cytosolic free Ca (2+) to control levels.ATP did not activate Ca (2+)-dependent K (+) currents, but did elicit Ca (2+)-independent K (+) currents, in cells dialyzed with ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The delay of activation of Ca (2+)-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 Ca (2+)-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 Ca (2+)-independent ATP-elicited response from a sustained to a transient one. A phospholipase C inhibitor, U73122 (1 microM), was shown to abolish the delayed ATP-elicited response. These results indicate that the second phase of the ATP-elicited response was a delayed Ca (2+)-independent K (+) current activated by exogenous ATP. This phase might represent a new vasoregulatory pathway in vascular smooth muscle cells. |
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