title: The acid-sensitive potassium channel TASK-1 in rat cardiac muscle.
abstract: OBJECTIVE
  The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes.
  
  
  METHODS
  Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293.
  
  
  RESULTS
  TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) by 31+/-3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil.
  
  
  CONCLUSIONS
  Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.
authors: Klinik für Anästhesiologie, Universitätsklinikum Marburg, 35033 Marburg, Germany.
authors: Caroline
authors: C
authors: Putzke
authors: Konstantin
authors: K
authors: Wemhöner
authors: Frank B
authors: FB
authors: Sachse
authors: Susanne
authors: S
authors: Rinné
authors: Günter
authors: G
authors: Schlichthörl
authors: Xian Tao
authors: XT
authors: Li
authors: Lucas
authors: L
authors: Jaé
authors: Ines
authors: I
authors: Eckhardt
authors: Erhard
authors: E
authors: Wischmeyer
authors: Hinnerk
authors: H
authors: Wulf
authors: Regina
authors: R
authors: Preisig-Müller
authors: Jürgen
authors: J
authors: Daut
authors: Niels
authors: N
authors: Decher
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D008729:Methoxamine / Q000494:pharmacology; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods; D014982:Xenopus laevis
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D009419:Nerve Tissue Proteins; D010879:Piperazines; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C057446:5-methylurapidil; C420132:potassium channel subfamily K member 3; D008729:Methoxamine