title: [Acetylcholine induces hyperpolarization independent of NO-release in guinea pig spiral modiolar artery].
abstract: OBJECTIVE
  Acetylcholine(ACh) is a neurotransmitter and a potent vasodilator in many vascular beds. ACh hyperpolarizes the smooth muscle cells(SMCs) of arteries including the cochlear spiral modiolar artery(SMA) via an endothelium-dependent mechanism, but the biochemical and biophysical basis of the hyperpolarization and vasodilation remain unclear and controversial.
  
  
  METHODS
  Using intracellular recording techniques and an in vitro preparation of the SMA, the ionic mechanism of the hyperpolarization and a possible role of nitric oxide(NO) were investigated.
  
  
  RESULTS
  With 5 mmol/L K(+) in the bathing solution and a minimum longitudinal tension, ACh (0.1-10 micromol/L) induced a robust hyperpolarization in low RP cells but caused a depolarization in the high RP cells. The ACh hyperpolarization was fast in onset and offset and the amplitude was concentration-dependent(22 and 30 mV by 1 micromol/L and 10 micromol/L ACh, respectively, n = 7 ). ACh also hyperpolarized the cells that initially had a high resting potential (RP) but were pre-depolarized by Ba(2+) (50-100 micromol/L). The onset time courses of the hyperpolarization were often slower in these cases than those without the presence of Ba(2+) . The ACh-induced hyperpolarization was blocked by atropine (0.1- 1 micromol/L, n = 6) or DAMP (50 -100 nmol/L, n = 6, a selective M3 antagonist) and also by BAPTA-AM (10 micromol/L, n = 7, a membrane-permeable Ca(2+)-chelator), or charybdotoxin plus apamin (50-100 nmol/L, n= 4, Ca(2+) -activated K(+) -channel blockers), but not by Nomega-nitro-L-arginine methyl ester (L-NAME, 300 micromol/L, n = 8, an inhibitor of NO-synthase), glipizide (10 micromol/L, n = 4, ATP-sensitive K(+) -channel blocker) and indomethacin (10 micromol/L, n = 4, cyclo-oxygenase inhibitor).
  
  
  CONCLUSIONS
  It is concluded that ACh-induced hyperpolarization in the arterial SMCs is primarily due to an activation of calcium-activated potassium channels via M3 receptors of endothelial cell and is independent of NO-release in the spiral modiolar artery.
authors.affiliation: Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Xinjiang.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Jun-Qiang
authors.initials: JQ
authors.lastname: Si
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001158:Arteries; D016764:Cell Polarity / Q000502:physiology; D003051:Cochlea / Q000098:blood supply / Q000502:physiology*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism
chemical_list: D024681:Potassium Channels, Calcium-Activated; D043587:Receptor, Muscarinic M3; D009569:Nitric Oxide; D000109:Acetylcholine