EFFECT OF ISOSORBIDDINITRATE ON EXOGENOUSLY EXPRESSED SLOWLY ACTIVATING K+ CHANNELS AND ENDOGENOUS K+ CHANNELS IN XENOPUS OOCYTES

1. The effects of isosorbiddinitrate (ISDN) were tested on membrane cu rrents and resting potential in Xenopus laevis oocytes which were eith er uninjected or injected with cRNA encoding for K+ channels from thre e distinct families (slowly activating I-sK channels, delayed-rectifyi ng Kv1.1 or inwardly rectifying IRK1 K+ channels). 2. In uninjected oo cytes ISDN (1 mM) resulted in a decrease of the holding current at pot entials more positive than -100 mV and in an increase at potentials be low -100 mV. Increasing extracellular K+ to 100 mM shifted the reversa l potential for ISDN-mediated effects to approximately -12 mV, suggest ing an inhibition of a K+ conductance by ISDN. 3. In current clamp stu dies ISDN (1 mM) and Ba2+ (3 mM) depolarized cell membrane. ISDN and B a2+ had no additive effects on membrane potential when applied simulta neously. In voltage clamp studies, corresponding results were observed for the effects of ISDN and Ba2+ on the holding current with an appar ent K-m of 0.21 and 0.08 mM, respectively. 4. In contrast to ISDN, the nitric oxide (NO) donors isosorbidmononitrate (ISMN) and S-nitrosocys teine (SNOC) had no effects on the holding currents in Xenopus oocytes . Moreover, the guanylate inhibitor LY 83583 did not affect ISDN-media ted holding current alterations, suggesting that ISDN acts independent ly of the second messenger NO. 5. ISDN inhibited exogenously expressed I-sK channels with an apparent K-m of 0.15 mM, but at 1 mM only weakl y inhibited Kv1.1 and IRK1 channels. 6. It is concluded that ISDN inhi bits an endogenous K+ conductance in Xenopus oocytes with a similar po tency to that shown by expressed I-sK channels. These effects are inde pendent of the second messenger NO.