Coupling excitation-contraction

Calcium plays a vital role ia excitation—contraction coupling, and failure to maintain iatraceUular calcium homeostasis results ia ceU death. The avaUabUity of the calcium antagonists also provides a powerful tool for basic studies of excitation—contraction coupling, stimulus—excretion coupling, and other specific physiological functions. 

Fleischer, S., and Iiini, M., 1989. Biochemistry and biophysics of excitation—contraction coupling. Annual Review of Biophysics and Biophysical Chemistry 18 333—364. 

Excitation-contraction coupling (EC coupling) is the mechanism underlying transformation of the electrical event (action potential) in the sarcolemma into the mechanical event (muscle contraction) which happens all over the muscle. In other words, it is the mechanism governing the way in which the action potential induces the increase in the cytoplasmic Ca2+ which enables the activation of myofibrils. 

Ogawa Y, Kurebayashi N, Murayama T (1999) Ryanodine receptor isoforms in excitation-contraction coupling. Adv Biophys 36 27-64... 

Somlyo, A., Somlyo, A.V. (1989). Flash photolysis studies of excitation-contraction coupling. Arm. Rev. Physiol. 52, 857-875. 

Four different localizations of fatigue can be identified (a) decreased central command (b) decreased activation of the muscle membrane and the T-tubular system (c) decreased Ca release from the SR and (d) decreased response to the Ca release by the contractile proteins. The first two are partly extra-muscular while c and d are intramuscular responses to the excitation of the muscle membrane and often defined as excitation-contraction coupling. 

From this brief summary of excitation-contraction coupling it is obvious that Ca is an important link between the activated membrane and the contractile proteins, and thus a regulator of tension development. Westerblad et al. (1991) defined three factors which explain the force decrease in fatigued muscle reduced Ca " release from the SR, reduced Ca sensitivity of the myofilaments, and reduced maximum Ca -activated tension. 

It has been shown that inositol triphosphate (IP3) is involved in the excitation-contraction coupling in smooth muscle (Vergara et al., 1985), but presently no clear evidence has been reported for a similar involvement in skeletal muscle. If IP3 functions as a messenger for Ca release, it would bridge the gap between muscle metabolic changes and Ca release, as ATP is a prerequisite for IP3 regeneration. 

Schneider, M.F. Chandler, W.K. (1973). Voltage dependent charge movement in skeletal muscle A possible step in excitation-contraction coupling. Nature 242,244-246. 

Vergara, J., Tsien, R.Y., Delay, M. (1985). Inositol 1,4, 5-trisphosphate Possible chemical link in excitation-contraction coupling in muscle. Proc. Natl. Acad. Sci. USA 82,6352-6356. 

A different but very interesting scenario involving L-type Ca channels is seen in skeletal muscle, where the major component of these Ca channels plays two roles. Skeletal muscle does not require extracellular Ca for excitation-contraction coupling, rather it utilizes Ca stored in the sarcoplasmic reticulum. The role of the L-type channel proteins as true Ca channels in skeletal muscle appears to be of secondary importance, but may be to provide Ca to the cells over longer periods of time. The main role of the L-type channel protein(s)... 

Key findings that demonstrated that the 0 subunit is the essential component of L-type channels have come from studies of the channel activity of the expressed protein. Expression studies performed in mammalian liver fibroblasts have demonstrated that the oti subunit alone can form a channel [77] and contains the receptors for the DHPs, PAAs and diltiazem [64]. In very elegant studies using a mouse model of muscular dysgenesis it has been demonstrated that the ] subunit DNA can restore Ca currents and the charge movement that arises from the voltagesensing function of the channels to the mutant cells that normally lack these activities [21,78,79]. The restoration of these activities restores excitation-contraction coupling. Thus it is clear that the aj subunit is the major functional unit of L-type Ca channels. 

Bers, D.M. (1991). Excitation-Contraction Coupling and Cardiac Contractile Force . Kluwer Academic Publishers, Dordrecht. 

FIGURE 43-6 Molecular physiology of musde excitation-contraction coupling. 

What is the role of intracellular Ca2+ waves due to Ca2+ release from the SR In many cell types stimulation results in Ca2+ waves rather than a maintained increase of [Ca2+] . Summation of such waves in many cells can result in a maintained contraction. Indeed, recent work suggests that these waves are implicated in the genesis of vascular tone (Peng et al 2001). It is important for us to consider how widespread in smooth muscle excitation-contraction coupling are such waves. 

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Cheng H, Lederer WJ, Cannell MB 1993 Calcium sparks elementary events underlying excitation—contraction coupling in heart muscle. Science 262 740—744 Collier ML, Thomas AP, Berlin JR 1999 Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+ release events in rat ventricular myocytes. J Physiol (Lond)... 

Nakai J, Tanabe T, Konno T, Adams B, Beam KG 1998 Localization in the II—III loop of the dihydropyridine receptor of a sequence critical for excitation-contraction coupling. J Biol Chem 273 24983-24986. 

Tanabe T, Beam KG, Adams BA, Niidome T, Numa S 1990 Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling. Nature 346 567-569... 

Calcium release events in excitation-contraction coupling in smooth muscle... 

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