title: The activation of Ca(2+)-dependent K+ conductance by adrenaline in mouse peritoneal macrophages.
abstract: Responses to adrenaline in mouse peritoneal macrophages were investigated with perforated and cell-attached patch-clamp recording, and with a combination of the perforated-patch recording and fura-2 fluorescence measurements. Extracellularly applied adrenaline induced a transient outward current (4-10 s in duration, 100-500 pA in amplitude) at -40 mV associated with a marked increase in conductance. The adrenaline-induced current [Io (Adr)] reversed polarity near -80 mV. The reversal potential depended distinctly on the external K+ concentration but not on external Cl- concentration. Removal of external Ca2+ did not affect Io(Adr) within 2-4 min but subsequent responses to adrenaline were progressively depressed. In contrast, treatment with an intracellular Ca2+ chelator, the acetoxymethyl ester of 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid completely abolished Io(Adr). Furthermore, Io(Adr) was blocked by bath-applied quinidine and charybdotoxin, but not by tetraethylammonium or apamin. Extracellular application of an alpha 1-adrenoceptor agonist phenylephrine and of noradrenaline mimicked Io(Adr). On the other hand, Io(Adr) was antagonized by a non-selective alpha-adrenoceptor antagonist phentolamine (0.2 microM) and an alpha 1-adrenoceptor antagonist prazosin (0.2 microM), but was not affected by an alpha 2-adrenoceptor antagonist yohimbine (1 microM) or a beta-adrenoceptor antagonist propranolol (1 microM). Cell-attached single-channel recordings with the pipette solution containing 145 mM KCl revealed the activation of single-channel currents with a conductance of 40 pS during application of adrenaline outside the patch. Parallel measurements of membrane current and fura-2 fluorescence in the same cell demonstrated a correlation between the rise in [Ca2+]i and an increase in K+ conductance. Therefore, it is concluded that adrenaline activates a Ca(2+)-dependent K+ conductance by release of Ca2+ from internal stores through an activation of an alpha 1-adrenoceptor.
authors.affiliation: Department of Physiology, Shimane Medical University, Izumo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: M
authors.initials: M
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Maeno
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004553:Electric Conductivity; D004837:Epinephrine / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009994:Osmolar Concentration; D010529:Peritoneal Cavity / Q000166:cytology*; D011188:Potassium / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
chemical_list: D011942:Receptors, Adrenergic, alpha; D011188:Potassium; D002118:Calcium; D004837:Epinephrine