Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor

1 Taurine is a sulphonic aminoacid present in high amounts in various tissu es including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and antischaemic effects. The cellular mech anism of action of taurine is under investigation and appears to involve th e interaction of the sulphonic aminoacid with several ion channels. 2 Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K+ channel (K-ATP) immediately afte r excision and on channels that underwent rundown. 3 The cytoplasmic application of 20 mM of taurine reduced the K-ATP current ; this effect was reverted by washout of the drug solution. In this experim ental condition the IC50 was 20.1 mM. After rundown, taurine inhibited the KATP current with similar efficacy. Competition experiments showed that tau rine shifted the dose-response inhibition curve of glybenclamide to the lef t on the log-dose axis without significantly affecting those of ATP or Ca2 ion. 4 Single channel recording revealed that taurine affects the close state of the channel prolonging it and reducing the bursts duration. 5 Our data indicate that taurine inhibits the muscular K-ATP channel interf ering with the glybenclamide site on the sulphonylurea receptor of the chan nel or on the site allosterically coupled to it. During ischaemia and hypox ia, the skeletal and heart muscles undergo several changes; for example, th e activation of K-ATP channels and loss of the intracellular taurine conten t. The depletion of taurine during ischaemia would contribute to the early activation of K-ATP channels and salvage the intracellular ATP content.