title: Effect of isosorbiddinitrate on exogenously expressed slowly activating K+ channels and endogenous K+ channels in Xenopus oocytes.
abstract: 1. The effects of isosorbiddinitrate (ISDN) were tested on membrane currents and resting potential in Xenopus laevis oocytes which were either uninjected or injected with cRNA encoding for K+ channels from three distinct families (slowly activating IsK channels, delayed-rectifying Kv1.1 or inwardly rectifying IRK1 K+ channels). 2. In uninjected oocytes ISDN (1 mM) resulted in a decrease of the holding current at potentials more positive than -100 mV and in an increase at potentials below -100 mV. Increasing extracellular K+ to 100 mM shifted the reversal potential for ISDN-mediated effects to approximately -12 mV, suggesting an inhibition of a K+ conductance by ISDN. 3. In current clamp studies ISDN (1 mM) and Ba2+ (3 mM) depolarized cell membrane. ISDN and Ba2+ had no additive effects on membrane potential when applied simultaneously. In voltage clamp studies, corresponding results were observed for the effects of ISDN and Ba2+ on the holding current with an apparent K(m) of 0.21 and 0.08 mM, respectively. 4. In contrast to ISDN, the nitric oxide (NO) donors isosorbidmononitrate (ISMN) and S-nitrosocysteine (SNOC) had no effects on the holding currents in Xenopus oocytes. Moreover, the guanylate inhibitor LY 83583 did not affect ISDN-mediated holding current alterations, suggesting that ISDN acts independently of the second messenger NO. 5. ISDN inhibited exogenously expressed IsK channels with an apparent K(m) of 0.15 mM, but at 1 mM only weakly inhibited Kv1.1 and IRK1 channels. 6. It is concluded that ISDN inhibits an endogenous K+ conductance in Xenopus oocytes with a similar potency to that shown by expressed IsK channels. These effects are independent of the second messenger NO.
authors.affiliation: Institute of Physiology, Eberhard-Karls-Universität Tübingen, Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
authors.forename: H G
authors.initials: HG
authors.lastname: Kopp
authors.forename: S
authors.initials: S
authors.lastname: Waldegger
authors.forename: I
authors.initials: I
authors.lastname: Samarzija
authors.forename: H
authors.initials: H
authors.lastname: Süssbrich
authors.forename: G
authors.initials: G
authors.lastname: Raber
authors.forename: K
authors.initials: K
authors.lastname: Kunzelmann
authors.forename: J P
authors.initials: JP
authors.lastname: Ruppersberg
authors.forename: F
authors.initials: F
authors.lastname: Lang
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018075:RNA, Complementary / Q000096:biosynthesis; D051381:Rats; D026403:S-Nitrosothiols; D014665:Vasodilator Agents / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D018075:RNA, Complementary; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D001464:Barium; C041715:6-anilino-5,8-quinolinedione; C021315:S-nitrosocysteine; D006162:Guanylate Cyclase; D007548:Isosorbide Dinitrate; D003545:Cysteine; C030397:isosorbide-5-mononitrate