Vol. 298, Issue 3, 1167-1171, September 2001

Voltage-Dependent Antagonist/Agonist Actions of Taurine on Ca²⁺-Activated Potassium Channels of Rat Skeletal Muscle Fibers

Domenico Tricarico, Mariagrazia Barbieri and Diana Conte Camerino

Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy

Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K⁺ channels, ATP-sensitive K⁺ channels, and voltage-dependent K⁺ channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca²⁺-activated K⁺ (K_Ca²⁺) channels, which are widely expressed in various tissues, including skeletal muscle. In the present work, the effects of taurine on K_Ca²⁺ channels of rat skeletal muscle fibers were investigated using the patch-clamp technique. The application of the amino acid to the internal side of the excised macropatches induced a dose-dependent decrease in the outward K_Ca²⁺ currents recorded at positive membrane potentials in the presence of 8 to 16 µM concentrations of free Ca²⁺ ions in the bath with an IC₅₀ of 31.9 · 10³ ± 1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane potentials taurine caused an enhancement of the muscular inward K_Ca²⁺ currents with a DE₅₀ (drug concentration needed to enhance the current by 50%) of 46.7 · 10³ ± 2 M (slope factor = 1.3) (n = 9 patches). Single channel analysis revealed that this effect was mediated by changes in the reversal potential of the K_Ca²⁺ channel for K⁺ ions with no changes in the gating properties or in the sensitivity of the channel to Ca²⁺ ions. Taurine also did not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on K_Ca²⁺ channels, being an inhibitor of the channel at positive membrane potentials and an activator at negative membrane potentials.