A delayed ATP‐elicited K+ current in freshly isolated smooth muscle cells from mouse aorta

• Published in: British journal of pharmacology Vol. 147; no. 1; pp. 45 - 54
• Main Authors: Serir, Karima, Hayoz, Sebastien, Fanchaouy, Mohammed, Bény, Jean‐Louis, Bychkov, Rostislav
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2006; Nature Publishing; Nature Publishing Group
• Subjects: Adenosine Triphosphate - physiology; Animals; Aorta - cytology; Aorta - metabolism; Aortic smooth muscle cells; ATP, GDPβs; Biological and medical sciences; Ca2+‐independent K+ current; Cells, Cultured; intracellular Ca2; Medical sciences; Mice; Myocytes, Smooth Muscle - metabolism; Pharmacology. Drug treatments; PLC blocker; Potassium - metabolism; purine receptors; Vasodilation - physiology; Purine derivatives; Calcium; Rodentia; Smooth muscle; Inorganic element; In vitro; Artery; GDPβs; Ca2+-independent K+ current; purine receptors; PLC blocker; Vertebrata; Mammalia; Mouse; Animal; Blood vessel; Aorta; Aortic smooth muscle cells; intracellular Ca2+; ATP; Circulatory system; Intracellular; ATP; Potassium; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706432

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