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 (approximately +0.02 to approximately +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.
Department of Zoology, La Trobe University, Bundoora, Victoria, 3083, Australia. dutka@zoo.latrobe.edu.au
Travis L
TL
Dutka
Graham D
GD
Lamb
D000818:Animals; D002336:Carnosine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans
D002336:Carnosine