Previous data have indicated that the chromanol 293B blocks a cAMP activated K⁺conductance in the colonic crypt, a K⁺conductance in pig cardiac myocytes and the K⁺conductance induced by IsK protein expression inXenopusoocytes. We have also shown that cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) up-regulates, apart from the typical Cl^–current, a 293B- inhibitable K⁺current. Very recently it has been shown that the IsK protein interacts with K_VLQT subunits to produce a K⁺channel. These data have prompted us to ask the following questions: Is the 293B-inhibitable current in oocytes expressing CFTR and activated by cAMP caused by an endogenous Xenopus K_VLQT (XK_VLQT), and is mouse K_VLQT (mK_VLQT) expressed in oocytes inhibited by 293B? Antisense and sense probes for XK_VLQT were coinjected with CFTR cRNA into oocytes. After 3–4 days the oocytes were examined by two electrode voltage clamp. It was found that in control oocytes expressing CFTR and stimulated by isobutylmethylxanthine (IBMX, 1 mmol/l) 293B (10 μmol/l) reduced the conductance (G_m). In oocytes coinjected with the sense probe for XK_VLQT and pretreated with IBMX 293B still reduced G_m, whilst the 293B-inhibitable G_mwas almost completely absent in oocytes coinjected with XK_VLQT antisense. In another series a full length clone for mK_VLQT was generated by PCR techniques and the cRNA was injected into oocytes. After several days these oocytes, unlike water injected ones, were found to be strongly hyperpolarized and their G_mwas increased significantly. The oocytes were depolarized significantly and their G_mwas reduced reversibly by 10 μmol/l 293B. These data indicate that CFTR activation by IBMX indeed co-activates an endogenous oocyte XK_VLQT channel and that this channel is inhibited by a new class of channel blockers, of which 293B is the prototype.

Authors and Affiliations

1. Physiologisches Institut der Albert-Ludwigs-Universität, Hermann-Herder-Straße 7, D-79104 Freiburg, Germany, , , , , , DE

   M. Bleich, M. Briel, R. Greger & K. Kunzelmann

2. Physiologisches Institut der Eberhard-Karls-Universität, Gmelinstr. 5, D-72076 Tübingen, Germany, , , , , , DE

   A. E. Busch

3. Hoechst AG, HMR TA Cardiovascular Agents, Geb. 838, D-65926 Frankfurt/Main, Germany, , , , , , DE

   H. J. Lang, U. Gerlach & H. Gögelein

Received: 8 April 1997 / Accepted: 23 May 1997

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