It seems that the sequence starts with a physical interaction between some of the DHPRs and some of the Ca 2+ release channels ( Tanabe et al. In particular, it is not known exactly what happens when the DHPRs open the Ca 2+ release channels, and what processes reinforce, inhibit or terminate the Ca 2+ release.
Though the overall sequence is clear, many important aspects of the process are not well understood. The AP depolarises the transverse tubular (T-) system, activating voltage sensors (dihydropyridine receptors, DHPRs) in the T-system membrane, which in turn somehow open the Ca 2+ release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum (SR), allowing Ca 2+ to flow into the cytoplasm and activate the contractile apparatus by binding to troponin-C (TnC). This constancy in Ca 2+ release should help ensure precise regulation of force production in fast-twitch muscle in a range of circumstances.Īn action potential (AP) elicits contraction in a vertebrate skeletal muscle fibre in a sequence of events known as excitation-contraction (E-C) coupling ( Melzer et al. This was also found to be the case in toad twitch fibres. These results show that the amount of Ca 2+ released by AP stimulation in rat fast-twitch fibres normally stays virtually constant over a wide range of SR Ca 2+ content, in spite of the likely large change in the electrochemical gradient for Ca 2+. When the SR was loaded maximally, increasing the above 280 μM resulted in an increase in the amount of Ca 2+ released per AP, probably because the greater level of cytoplasmic Ca 2+ buffering prevented Ca 2+ inactivation from adequately limiting Ca 2+ release. Consistent with this, successive APs (15 s apart) elicited similar amounts of Ca 2+ release ≈10–16 times before the amount released declined, and the SR was fully depleted of Ca 2+ after a total release calculated to be ≈3–4 mM. When the SR was loaded to near-maximal capacity (≈3–4 mM), each AP (or pair of APs 10 ms apart) still only released approximately the same amount of Ca 2+ as that released when the fibre was endogenously loaded. When Ca 2+ reuptake was blocked, APs applied 15 s apart elicited similar amounts of Ca 2+ release (≈230 μM) on the first two or three occasions and then progressively less Ca 2+ was released until the SR was fully depleted after a total of approximately eight APs. If a second AP was elicited 10 ms after the first, only a further ≈60 μM Ca 2+ was released, the reduction probably being due to Ca 2+ inactivation of Ca 2+ release. In a fibre with the SR loaded with Ca 2+ at the endogenous level (≈1.2 mM, expressed as total Ca 2+ per litre fibre volume approximately one-third of maximal loading), a single AP triggered the release of ≈230 μM Ca 2+. When Ca 2+ reuptake was blocked, an estimate of the amount of Ca 2+ released by an AP could be derived from the size of the force response. Responses were elicited in the presence of known amounts (0–0.38 mM) of BAPTA, a fast Ca 2+ buffer, with the SR Ca 2+ pump either functional or blocked by 50 μM 2,5-di-tert-butyl-1,4-hydroquinone (TBQ). Single muscle fibres were mechanically skinned and electric field stimulation was used to induce an AP in the transverse-tubular system and a resulting twitch response. This study examined the relationship between the level of Ca 2+ loading in the sarcoplasmic reticulum (SR) and the amount of Ca 2+ released by an action potential (AP) in fast-twitch skeletal muscle fibres of the rat.
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