title: Channels involved in transient currents unmasked by removal of extracellular calcium in cardiac cells.
abstract: In cardiac cells that lack macroscopic transient outward K(+) currents (I(to)), the removal of extracellular Ca(2+) can unmask "I(to)-like" currents. With the use of pig ventricular myocytes and the whole cell patch-clamp technique, we examined the possibility that cation efflux via L-type Ca(2+) channels underlies these currents. Removal of extracellular Ca(2+) and extracellular Mg(2+) induced time-independent currents at all potentials and time-dependent currents at potentials greater than -50 mV. Either K(+) or Cs(+) could carry the time-dependent currents, with reversal potential of +8 mV with internal K(+) and +34 mV with Cs(+). Activation and inactivation were voltage dependent [Boltzmann distributions with potential of half-maximal value (V(1/2)) = -24 mV and slope = -9 mV for activation; V(1/2) = -58 mV and slope = 13 mV for inactivation]. The time-dependent currents were resistant to 4-aminopyridine and to DIDS but blocked by nifedipine at high concentrations (IC(50) = 2 microM) as well as by verapamil and diltiazem. They could be increased by BAY K-8644 or by isoproterenol. We conclude that the I(to)-like currents are due to monovalent cation flow through L-type Ca(2+) channels, which in pig myocytes show low sensitivity to nifedipine.
authors.affiliation: Laboratory of Cardiac Cellular Research, Centre for Experimental Surgery and Anaesthesiology, University of Leuven, Belgium.
authors.forename: Regina
authors.initials: R
authors.lastname: Macianskiene
authors.forename: Francesco
authors.initials: F
authors.lastname: Moccia
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
authors.forename: Willem
authors.initials: W
authors.lastname: Flameng
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002586:Cesium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004351:Drug Resistance; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000008:administration & dosage; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D011943:Receptors, Adrenergic, beta; D002586:Cesium; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015761:4-Aminopyridine; D014700:Verapamil; D004110:Diltiazem; D008274:Magnesium; D009543:Nifedipine; D007545:Isoproterenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D002118:Calcium