title: Alpha 1-adrenoceptors reduce background K+ current in rabbit ventricular myocytes.
abstract: 1. Ventricular myocytes were isolated by enzymatic dispersion of adult rabbit hearts, and voltage clamped using the whole-cell variation of the patch clamp technique. Experiments were carried out at either 35 degrees C or room temperature (21-23 degrees C). 2. In the presence of 10(-3) M-4-aminopyridine to block the transient outward K+ current, and 10(-6) M-propranolol to block beta-adrenoceptors, the alpha 1-adrenergic agonist methoxamine produced action potential prolongation, and a small depolarization of the diastolic membrane potential. Under voltage clamp conditions, methoxamine decreased the magnitude of the inward rectifier K+ current, IK1, in both the inward and outward directions. This effect was dose dependent (10(-5)-10(-3) M) and fully reversible upon wash-out of the agonist. 3. The neurotransmitter noradrenaline (10(-6)-2 x 10(-5) M), in the presence of propranolol (10(-6) M), also reduced IK1 in ventricular cells, and this effect was blocked by the specific alpha 1-adrenoceptor antagonist prazosin. 4. The alpha 1-adrenoceptor-mediated decrease in IK1 in ventricular myocytes was not affected by pre-incubation of the cells with 0.5 micrograms/ml pertussis toxin (8-10 h, 30-32 degrees C). This result suggests that in rabbit ventricular cells, the alpha 1-modulation of IK1 occurs via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein. 5. These observations demonstrate that IK1 in ventricular myocytes can be modulated by cardiac alpha 1-adrenoceptors. The resulting changes in action potential repolarization and diastolic membrane potential may have significant effects on cardiac performance.
authors.affiliation: Department of Medical Physiology, University of Calgary, Alberta, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Fedida
authors.forename: A P
authors.initials: AP
authors.lastname: Braun
authors.forename: W R
authors.initials: WR
authors.lastname: Giles
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D011433:Propranolol; D015761:4-Aminopyridine; D037342:Pertussis Toxin; D000254:Sodium-Potassium-Exchanging ATPase; D008729:Methoxamine; D009638:Norepinephrine; D011224:Prazosin