Voltage-dependent antagonist/agonist actions of taurine on Ca2+-activated potassium channels of rat skeletal muscle fibers

Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K+ channels, ATP-sensitive K+ chann els, and voltage-dependent K+ channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca2+-activated K+ (KCa 2+) channels, which are widely expressed in various tissues, including skeleta l muscle. In the present work, the effects of taurine on KCa 2+ channels of rat skeletal muscle fibers were investigated using the patch-clamp techniq ue. The application of the amino acid to the internal side of the excised m acropatches induced a dose-dependent decrease in the outward KCa 2- current s recorded at positive membrane potentials in the presence of 8 to 16 muM c oncentrations 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 KCa 2+ cur rents 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 KCa 2+ channel for K+ ions with no changes in the gating p roperties or in the sensitivity of the channel to Ca2+ ions. Taurine also d id not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on KCa 2+ channels, being an inhibitor of the channel at positive membrane potentials and an activator at negativ e membrane potentials.