title: Contribution of potassium accumulation in narrow extracellular spaces to the genesis of nicorandil-induced large inward tail current in guinea-pig ventricular cells.
abstract: The mechanism of nicorandil-induced large inward tail current (Itail) in single guinea-pig ventricular cells was investigated using the whole-cell patch-clamp technique. In the presence of 0.5-1.0 mM nicorandil, an activator of adenosine 5'-triphosphate (ATP)-sensitive K+ current (IKATP), a depolarization pulse causing a large outward current was followed by a large inward Itail on the repolarization step to the holding potential at -85 mV. The larger the outward current, the greater the Itail. The amplitude of Itail increased as a single exponential function (tau = 74.9 ms) as the duration of preceding depolarization was prolonged. Both the outward current and Itail were inhibited nearly completely after application of glibenclamide (1 microM), a specific blocker of IKATP. Substitution of K+ with Cs+ in both the external and internal solutions resulted in a virtual elimination of Itail. Itail was well preserved under the condition where Ca2+ entry during the preceding depolarization was largely inhibited or where external Na+ was replaced by Li+. A transient positive shift of reversal potential for the net current was observed at the peak of Itail). At 30 mM external K+ concentration, Itail was almost eliminated. From these findings, its is concluded that the Itail is a K+ current associated with an alteration of the K+ equilibrium potential (EK) following a substantial K+ efflux. This EK change is most likely explained by an accumulation of K+ in transverse tubules (T-tubules) since Itail was not induced in atrial cells in which T-tubules are poorly developed.
authors.affiliation: Department of Circulation, Nagoya University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yasui
authors.forename: T
authors.initials: T
authors.lastname: Anno
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
authors.forename: M R
authors.initials: MR
authors.lastname: Boyett
authors.forename: I
authors.initials: I
authors.lastname: Kodama
authors.forename: J
authors.initials: J
authors.lastname: Toyama
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000502:physiology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D011188:Potassium / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium