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

Abstract

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 · 10⁻³ ± 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 · 10⁻³ ± 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.