title: Sympathetic control of arterial membrane potential by ATP-sensitive K(+)-channels.
abstract: Stimulation of perivascular nerve terminals leads to a release of various neurotransmitters such as norepinephrine, epinephrine, acetylcholine, nitric oxide, and calcitonin gene-related peptide (CGRP). Because some of these substances have been shown to cause smooth muscle hyperpolarization by direct or endothelium-dependent mechanisms, we hypothesized that the liberation of 1 or more of these transmitters may lead to neurogenic hyperpolarization in arterial muscle cells. The present study was designed to determine the presence or absence of neurogenic hyperpolarization and, if present, its underlying mechanisms in isolated rat mesenteric resistance arteries, through the use of conventional microelectrode techniques. The experiments were performed under the combined blockade of alpha-adrenoceptors and purinoceptors with phentolamine and suramin to eliminate depolarizing responses to nerve stimulation. Under these conditions, perivascular nerve stimulation (5 Hz, 30 seconds) evoked smooth muscle hyperpolarization (-3.3+/-0.3 mV, n=15), which was abolished by tetrodotoxin, indicating the neurogenic origin of the response. This neurogenic hyperpolarization was resistant to atropine, nitro-L-arginine, or CGRP8-37, a CGRP antagonist, but was abolished by guanethidine and beta-blocker propranolol. This hyperpolarization was also abolished by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker, but was unaffected by apamin, a Ca(2+)-activated K(+) channel blocker. In separate experiments, exogenous norepinephrine caused glibenclamide-sensitive hyperpolarization in the presence of phentolamine. On the other hand, norepinephrine-induced depolarization in the absence of phentolamine was enhanced by propranolol. These findings suggest that neurally released catecholamines cause membrane hyperpolarization through the activation of K(ATP) by beta-adrenoceptors. Such hyperpolarization may play an important role in the control of arterial membrane potential by opposing alpha-adrenergic depolarization.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: I
authors.initials: I
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Fujishima
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000294:innervation* / Q000502:physiology; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000294:innervation* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D010276:Parasympatholytics; D015221:Potassium Channels; D013565:Sympatholytics; D013566:Sympathomimetics; D014665:Vasodilator Agents; D019335:Nitroarginine; D013779:Tetrodotoxin; D011189:Potassium Chloride; D001285:Atropine; D000255:Adenosine Triphosphate; D011433:Propranolol; D002211:Capsaicin; D005905:Glyburide; D009638:Norepinephrine; D010646:Phentolamine; D006145:Guanethidine