title: Norepinephrine-induced sustained inward current in brown fat cells: alpha(1)-mediated by nonselective cation channels.
abstract: The nature of the sustained norepinephrine-induced depolarization in brown fat cells was examined by patch-clamp techniques. Norepinephrine (NE) stimulation led to a whole cell current response consisting of two phases: a first inward current, lasting for only 1 min, and a sustained inward current, lasting as long as the adrenergic stimulation was maintained. The nature of the sustained current was here investigated. It could be induced by the alpha(1)-agonist cirazoline but not by the beta(3)-agonist CGP-12177A. Reduction of extracellular Cl(-) concentration had no effect, but omission of extracellular Ca(2+) or Na(+) totally eliminated it. When unstimulated cells were studied in the cell-attached mode, some activity of approximately 30 pS nonselective cation channels was observed. NE perfusion led to a 10-fold increase in their open probability (from approximately 0.002 to approximately 0.017), which persisted as long as the perfusion was maintained. The activation was much stronger with the alpha(1)-agonist phenylephrine than with the beta(3)-agonist CGP-12177A, and with the Ca(2+) ionophore A-23187 than with the adenylyl cyclase activator forskolin. We conclude that the sustained inward current was due to activation of approximately 30 pS nonselective cation channels via alpha(1)-adrenergic receptors and that the effect may be mediated via an increase in intracellular free Ca(2+) concentration.
authors.affiliation: The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden. Ari-Pekka.Kovisto@Orionpharm.com
authors.forename: A
authors.initials: A
authors.lastname: Koivisto
authors.forename: D
authors.initials: D
authors.lastname: Siemen
authors.forename: J
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002412:Cations; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012964:Sodium / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002412:Cations; D002712:Chlorides; D007093:Imidazoles; D007473:Ion Channels; D007476:Ionophores; D011412:Propanolamines; D018340:Receptors, Adrenergic, alpha-1; D005576:Colforsin; D010656:Phenylephrine; D000001:Calcimycin; D012964:Sodium; D000262:Adenylyl Cyclases; C014282:cirazoline; C033394:CGP 12177; D002118:Calcium; D009638:Norepinephrine