Effect of Carnosine on Excitation–Contraction Coupling in Mechanically-Skinned Rat Skeletal Muscle

This study investigated whether carnosine alters individual processes involved in normal excitation–contraction (E–C) coupling in mammalian skeletal muscle fibres. Mechanically-skinned fibre preparations were utilized because they allow carnosine to be precisely and readily applied to the cytoplasmic environment as desired, whilst still retaining the normal E–C coupling mechanism. Carnosine caused an increase (∼+0.02 to ∼+0.09 pCa units) in Ca2+-sensitivity of the contractile apparatus in a concentration-dependent manner (i.e. with 4, 8 and 16 mM respectively). Force responses elicited by 8 mM caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) were potentiated in the presence of carnosine (compared to the bracketing responses in the absence of carnosine). Force responses elicited by transverse tubular (T-) system depolarization via the dihydropyridine receptors (DHPRs), either by ionic (Na+) substitution or by action potentials (APs), were also potentiated in a concentration-dependent manner in the presence of carnosine. The potentiation of the force responses in all of the various experiments was seemingly totally explicable by the increase in Ca2+-sensitivity of the contractile apparatus caused by carnosine. Thus, these results show that carnosine potentiates force responses solely by 'sensitizing' the contractile apparatus to Ca2+ ions and under physiological conditions does not cause additional Ca2+ release from the SR.