EFFECTS OF ALMITRINE BISMESYLATE ON THE IONIC CURRENTS OF CHEMORECEPTOR CELLS FROM THE CAROTID-BODY

Almitrine is a drug used in the treatment of hypoxemic chronic lung di seases such as bronchitis and emphysema because it is a potent stimula nt of the carotid bodies in human and different animal species that pr oduces a long-lasting enhancement of alveolar ventilation, amelioratin g arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic curr ents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the p atch-clamp technique. Almitrine at concentrations up to 10 mu M did no t affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of almitrine significant ly inhibited the Ca2+-dependent component of K+ currents in rat chemor eceptor cells. This effect of almitrine on the Ca2+-dependent componen t of K+ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparatio n, almitrine inhibited the activity of a high-conductance (152 +/- 13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect was 0.22 mu M. The inhibitory effect of almi trine on Ca2+-dependent K+ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca2+-dependent K+ ch annel and that in rat chemoreceptor cells, this inhibition could repre sent an important mechanism of action underlying the therapeutic actio ns of the drug.