Potassium channel openers inhibit ATP-induced cytosolic free calcium increase in cultured rabbit aortic smooth muscle cells.
OBJECTIVE
To study the effects of potassium channel openers (PCO) on cytosolic free calcium ([Ca2+]i) changes and their possible mechanisms in vascular smooth muscle cells (VSMC).


METHODS
Cultured rabbit aortic VSMC were treated with Fura-2 AM 2.5 mumol.L-1 at 37 degrees C for 50 min. The PCO were pinacidil (Pin), nicorandil (Nic), lemakalim (Lem), and RP 49356 (RP). [Ca2+]i level was measured by fluorospectrometer.


RESULTS
[Ca2+]i increase induced by K+ 30 mmol.L-1 was weakly inhibited by Pin, Nic, Lem, and RP (441 +/- 23, 455 +/- 48, 451 +/- 22, 370 +/- 31 vs 544 +/- 40 nmol.L-1, P < 0.01). ATP (0.1 mmol.L-1)-induced peak and sustained [Ca2+]i increase were inhibited by these agents in a concentration-dependent manner. The effects of Pin, Lem, and RP were completely canceled (peak phase: 549 +/- 39, 540 +/- 30, 564 +/- 13 vs 541 +/- 39 nmol.L-1; sustained phase: 413 +/- 25, 364 +/- 16, 377 +/- 11 vs 380 +/- 8 nmol.L-1), but that of Nic was only partially blocked (peak phase: 453 +/- 31 vs 541 nmol.L-1; sustained phase: 348 +/- 19 vs 380 +/- 8 nmol.L-1, P < 0.01) by glibenclamide (Gli, 10 mumol.L-1). Pretreated with the Pin, Nic, Lem, and RP (10 mumol.L-1), the peak [Ca2+]i elevation induced by ATP was reduced in the Ca(2+)-free solution (129 +/- 17, 142 +/- 21, 136 +/- 14, 114 +/- 9 vs 258 +/- 32 nmol.L-1, P < 0.01).


CONCLUSIONS
Pin, Nic, Lem, and RP inhibited ATP-induced [Ca2+]i increase, associated with decreases of both Ca2+ release from intracellular store and Ca2+ influx from extracellular store.
Research Section of Pharmacology, Hu-nan Medical University, Changsha, China.
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DH
Shi
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Guo
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D019806:Cromakalim / Q000037:antagonists & inhibitors; D005905:Glyburide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D020108:Nicorandil / Q000037:antagonists & inhibitors*; D020110:Pinacidil / Q000037:antagonists & inhibitors*; D015221:Potassium Channels; D011817:Rabbits
D015221:Potassium Channels; D019806:Cromakalim; D020108:Nicorandil; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium