Inhibition by Barium and Glibenclamide of the Net Loss of 86Rb+ from Rabbit Myocardium During Hypoxia

Study Objective: The aim was to determine the effects of barium ions and glibenclamide on the hypoxia induced K+ efflux from rabbit myocardium.

Design: Experiments were performed on the isolated interventricular septum of the rabbit perfused with a physiological solution through the septal artery. The stimulation rate was 90 beats.min-1 and the temperature 32 degrees C. The flux of 86Rb+ was used as a surrogate of K+ fluxes.

Experimental Material: Septa were obtained from adult male New Zealand white rabbits.

Measurements And Main Results: The uptake of 86Rb+ by the septum could be fitted to a single exponential curve with a rate constant of 0.024(SEM 0.001) min-1 (n = 14). Washout experiments were performed in which septa were labelled with 86Rb+ and then perfused with unlabelled solution for 60 min. The rate constants for the efflux of 86Rb+ were similar and were 0.022(0.001) min-1 (n = 13) for radioactivity in the tissue and 0.029(0.001) min-1 (n = 13) for radioactivity in the effluent. These rate constants were similar to those reported previously for 42K+. Septa were labelled for 150 to 180 min with 86Rb+ and then perfused with a hypoxic substrate free solution for 15 min followed by reoxygenation. The net loss of 86Rb+ was calculated to be equivalent to 4.00(0.20) mmol.kg-1 wet tissue of K+ (n = 8) and in washout experiments (n = 6) this loss was shown to be due to increased efflux. Ba2+, 0.1 mM and 1.0 mM, added at the onset of hypoxia decreased net tissue loss of 86Rb+ by 64(6)% (n = 5) and 97(1)% (n = 6) respectively (both p less than 0.01). Glibenclamide (0.1 mM) decreased tissue net loss by 52(3)% (n = 6, p less than 0.01).

Conclusions: Part of hypoxia induced net K+ loss in this preparation can be attributed to activation of ATP sensitive K+ channels but other mechanisms are also involved.