title: IK of rabbit ventricle is composed of two currents: evidence for IKs.
abstract: The delayed rectifier K+ current (IK) in rabbit heart has long been thought to consist of only a single, rapidly activating, dofetilide-sensitive current, IKr. However, we find that IK of rabbit ventricular myocytes actually consists of both rapid and slow components, IKr and IKs, respectively, that can be isolated pharmacologically. Thus, after complete blockade of IKr with dofetilide, the remaining current, IKs, is homogeneous as judged by an envelope of tails test. IKs activates and deactivates slowly, continues to activate during sustained depolarizations, has a half-activation potential of 7.0 +/- 0.8 mV and slope factor of 11.0 +/- 0.7 mV, reverses at -77.2 +/- 1.3 mV (extracellular K+ concentration = 4 mM), is increased by removing extracellular K+, and is enhanced by isoproterenol and stocked by azimilide. Northern analysis demonstrates that the minK (IsK) gene, which encodes a subunit of the channel that underlies the IKs current, is expressed in rabbit heart. Expression of the rabbit protein in Xenopus oocytes elicits a slowly activating, voltage-dependent current, IsK, similar to those expressed previously from mouse, rat, guinea pig, and human genes. The results demonstrate that IKs is present in rabbit ventricle and therefore contributes to cardiac repolarization in this species.
authors.affiliation: Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA. joseph_salata@merck.com
authors.forename: J J
authors.initials: JJ
authors.lastname: Salata
authors.forename: N K
authors.initials: NK
authors.lastname: Jurkiewicz
authors.forename: B
authors.initials: B
authors.lastname: Jow
authors.forename: K
authors.initials: K
authors.lastname: Folander
authors.forename: P J
authors.initials: PJ
authors.lastname: Guinosso
authors.forename: B
authors.initials: B
authors.lastname: Raynor
authors.forename: R
authors.initials: R
authors.lastname: Swanson
authors.forename: B
authors.initials: B
authors.lastname: Fermini
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D015870:Gene Expression; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D006801:Humans; D006827:Hydantoins; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D016276:Ventricular Function; D014982:Xenopus laevis
chemical_list: D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; D015221:Potassium Channels; C086123:azimilide; D007545:Isoproterenol