EFFECT OF TAURINE DEPLETION ON EXCITATION-CONTRACTION COUPLING AND CL- CONDUCTANCE OF RAT SKELETAL-MUSCLE

The pharmacological action of taurine on skeletal muscle is to stabili ze sarcolemma by increasing macroscopic conductance to Cl- (G(Cl)), wh ereas a proposed physiological role for the amino acid is to modulate excitation-contraction coupling mechanism via Ca2+ availability. To ge t insight in the physiological role of taurine in skeletal muscle, the effects of its depletion were evaluated on voltage threshold for mech anical activation and G(Cl) with the two intracellular microelectrode method in 'point' voltage clamp mode and current clamp mode, respectiv ely. The experiments were performed on extensor digitorum longus muscl e fibers from rats depleted of taurine by a chronic 4 week treatment w ith guanidinoethane sulfonate, a known inhibitor of taurine transporte r. The treatment significantly modified the mechanical threshold of st riated fibers; i.e. at each pulse duration they needed significantly l ess depolarization to contract and the fitted rheobase voltage was mor e negative by 10 mV with respect to untreated muscle fibers. In parall el, the treatment with guanidinoethane sulfonate produced a significan t 40% lowering of G(Cl). In vitro application of 60 mM of taurine to s uch depleted muscles almost completely restored the mechanical thresho ld and increased G(Cl) even above the value of untreated control. Howe ver, in vitro application of 60 mM of either taurine or guanidinoethan e sulfonate to untreated control muscles did not cause any change of t he mechanical threshold but increased G(Cl) by 40% and 21%, respective ly. Furthermore, 100 mu M Of the S-(-) enantiomer of 2-(p-chlorophenox y)propionic acid almost fully blocked G(Cl) but did not produce any ch ange in the mechanical threshold of normal muscle fibers. The present results show that the large amount of intracellular taurine plays a ro le in the excitation-contraction coupling mechanism of striated muscle fibers. This action is independent from any effect involving muscle C l- channels, but it is likely mediated by the proposed ability of taur ine to modulate Ca2+ availability through the interaction with the Ca2 + transporters present on sarcoplasmic reticulum.