Vol. 53, Issue 2, 330-339, February 1998

Effects of Almitrine Bismesylate on the Ionic Currents of Chemoreceptor Cells from the Carotid Body

J. R. López-López, M. T. Pérez-García, E. Canet, and C. Gonzalez

Department of Biochemistry and Molecular Biology and Physiology, School of Medicine, University of Valladolid, 47005 Valladolid, Spain (J.R.L.-L., M.T.P.-G., C.G.), and Institute de Recherches Internationales Servier, Neully-sur-Seine, France (E.C.)

Almitrine is a drug used in the treatment of hypoxemic chronic lung diseases such as bronchitis and emphysema because it is a potent stimulant of the carotid bodies in human and different animal species that produces a long-lasting enhancement of alveolar ventilation, ameliorating arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic currents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the patch-clamp technique. Almitrine at concentrations up to 10 µM did not affect whole-cell voltage-dependent K⁺, Ca²⁺, or Na⁺ currents in rat or rabbit cells. However, this concentration of almitrine significantly inhibited the Ca²⁺-dependent component of K⁺ currents in rat chemoreceptor cells. This effect of almitrine on the Ca²⁺-dependent component of K⁺ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparation, 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 µM. The inhibitory effect of almitrine on Ca²⁺-dependent K⁺ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca²⁺-dependent K⁺ channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug.