Mechanisms underlying hyperpolarization evoked by P2Y receptor activation in mouse distal colon.
In murine colonic circular muscle, ATP mediates fast component of the nerve-evoked inhibitory junction potentials, via activation of P2Y receptors and opening of apamin-sensitive Ca2+-dependent K+ channels. We investigated, using microelectrode recordings, the intracellular events following P2Y-receptor activation by electrical field stimulation or by adenosine 5'-O-2-thiodiphosphate (ADPbetaS), ATP stable analogue. The fast-inhibitory junction potential amplitude was reduced by thapsigargin or ciclopiazonic acid (CPA), sarcoplasmic reticulum Ca2+-ATPase inhibitors, by ryanodine, which inhibits Ca2+ release from ryanodine-sensitive stores, and by 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), an adenylyl cyclase inhibitor. Fast-inhibitory junction potentials were enhanced by 2-aminoethoxy-diphenylborate (2-APB), an IP3 receptor inhibitor or by {1-[6((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione} (U-73122), a phospholipase C inhibitor. ADPbetaS induced hyperpolarization that was significantly reduced by apamin, thapsigargin, CPA, ryanodine, 2-APB and SQ 22,536, but it was not modified by U-73122. Forskolin, an adenylyl cyclase activator, induced hyperpolarization that was inhibited by SQ 22,536, apamin or ryanodine. In conclusion, in murine colon, apamin-sensitive hyperpolarization induced by activation of P2Y receptors is mainly mediated by release of Ca2+ from intracellular ryanodine-dependent stores via a mechanism involving adenylyl cyclase.
Zizzo
Maria Grazia
MG
Dipartimento di Biologia Cellulare e dello Sviluppo--Laboratorio di Fisiologia generale--Università di Palermo--Viale delle Scienze, 90128 Palermo, Italy.
Mulè
Flavia
F
Serio
Rosa
R
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*
D024681:Potassium Channels, Calcium-Activated; D018340:Receptors, Adrenergic, alpha-1; D018048:Receptors, Purinergic P2; D005576:Colforsin; D000262:Adenylyl Cyclases; D002118:Calcium