Events of the excitation–contraction–relaxation (E–C–R) cycle in fast- and slow-twitch mammalian muscle fibres relevant to muscle fatigue

The excitation–contraction–relaxation cycle (E–C–R) in the mammalian twitch muscle comprises the following major events: (1) initiation and propagation of an action potential along the sarcolemma and transverse (T)-tubular system; (2) detection of the T-system depolarization signal and signal transmission from the T-tubule to the sarcoplasmic reticulum (SR) membrane; (3) Ca²⁺ release from the SR; (4) transient rise of myoplasmic [Ca²⁺]; (5) transient activation of the Ca²⁺-regulatory system and of the contractile apparatus; (6) Ca²⁺ reuptake by the SR Ca²⁺ pump and Ca²⁺ binding to myoplasmic sites. There are many steps in the E–C–R cycle which can be seen as potential sites for muscle fatigue and this review explores how structural and functional differences between the fast- and slow-twitch fibres with respect to the E–C–R cycle events can explain to a great extent differences in their fatiguability profiles.     

Light–dependent effects of zinc protoporphyrin IX on endothelium–dependent relaxation resistant to NoM–nitro–L–arginine

Acetylcholine (ACh) induces an Nω–nitro–L–arginine (L–NOARG)–resistant relaxation and hyperpolarization in the rat isolated hepatic artery. The possibility that carbon monoxide (CO) produced by haem oxygenase (HO) is an endogenous mediator of this response was investigated. Exogenously applied CO evoked a concentration–dependent relaxation, and the CO ‘scavenger’ oxyhaemoglobin (10μM) reduced the maximum ACh–induced relaxation by 25%. The HO inhibitor zinc protoporphyrin IX (ZnPP, 10 μM virtually abolished the ACh–induced relaxation in experiments carried out under ordinary light conditions. However, ZnPP did not affect the ACh–induced relaxation under dark conditions, even after exposure of ZnPP to intense light before the preincubation period. Biliverdin (0.1 mM), a feedback inhibitor of HO, was also inactive under dark conditions, and the HO substrate haematin (0.1 mM) did not facilitate the ACh–induced relaxation. The relaxation induced by the nitric oxide (NO) donor 3–morpholino–sydnonimin was not affected by ZnPP in the presence of light. However, ZnPP inhibited the relaxation evoked by the potassium channel opener levcromakalim and the tonic component of the contractile response to 60 mM potassium, indicating that ZnPP has effects distinct from HO inhibition in the presence of light. ZnPP should therefore be protected from light when used to inhibit HO–mediated CO formation. The results do not suggest that CO generated by HO mediates the endothelium–dependent, L–NOARG–resistant relaxation induced by ACh in the rat hepatic artery.