The later and longer-lasting events (particularly, the thin filament de-activation due to Ca-uptake by SR) of course occur at the higher temperature. Thus, under steady state conditions, the E-C coupling events (voltage gating at the dihydropyridine receptors, Ca 2+ -release at the ryanodine receptors, thin filament activation/de-activation etc, see Franzini-Armstrong and Protasi, 1997 Stephenson et al., 1998 Lamb, 2002) and crossbridge cycling/force generation processes all occur at the same temperature, When a Tjump is placed on the rising phase, the tension is potentiated because one or more of the E-C coupling events, particularly, the excitation of the sarcolemma and T-system (and Ca 2+ -release from the SR that is tightly coupled to the depolarisation and the fast thin filament activation -see Baylor and Hollingworth, 2003) occur at the initial lower temperature, thus lessening their ''force-depressing effect'' on warming. Despite the uncertainties above, it would be of interest to examine whether the findings may arise due to different temperature-sensitivities of the various molecular processes that lead to a twitch contraction.
The normal coupling mechanism functions well in mammalian fast-twitch fibers even when the SR is only partially loaded, whereas CICR is highly dependent on SR luminal Ca2+ and caffeine is poorly effective at inducing release at the endogenous SR Ca2+ load level. The Ca2+ load in the SR of skinned fibers can be set at the endogenous level or otherwise. EC coupling is evidently not mediated by upmodulation of Ca2+-induced Ca2+ release (CICR) or by an oxidation or phosphorylation reaction. It was found that ATP has to be bound to the Ca2+ release channels for them to be activated by the voltage-sensors and that the coupling mechanism likely involves the voltage-sensors removing the inhibitory effects of cytoplasmic Mg2+ on the release channels such findings are relevant to the basis of muscle fatigue and to certain diseases such as malignant hyperthermia (MH). Twitch and tetanic force responses elicited in skinned fibers closely resemble those in intact fibers, showing that the coupling mechanism is entirely functional.
Important aspects of the excitation-contraction (EC) coupling process in skeletal muscle have been revealed using mechanically-skinned fibers in which the transverse-tubular system can be depolarized by ion substitution or electrical stimulation, activating the voltage-sensors which in turn open the Ca2+ release channels in the adjacent sarcoplasmic reticulum (SR).
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