Muscle structure sarcoplasmic reticulum

The sarcoplasmic reticulum (Figure 8.15) is a structure that surrounds each myofibril in muscle. The sarcoplasmic reticulum has a lumen within which it stores calcium ions. Upon stimulation by the nervous system, the sarcoplasmic reticulum depolarizes and releases calcium, which pours into the myofibrils and stimulates muscular contraction. 

This chapter will summarize recent developments on the structure of the Ca -ATPase of the sarcoplasmic reticulum with occasional references to the Ca -ATPases in the plasma membranes and endoplasmic reticulum of non-muscle cells. 

Our discussion here will concentrate on the various forms of the Ca " transport ATPases that occur in the sarcoplasmic reticulum of muscle cells of diverse fiber types and in the endoplasmic reticulum of nonmuscle cells (SERCA). The structure of these enzymes will be compared with the Ca transport ATPases of surface membranes (PMCA) [3,29-32,34] and with other ATP-dependent ion pumps that transport Na, K, andH [46,50-52]. 

The intracellular hgand-gated Ca " channels include the channels in endoplasmic and sarcoplasmic reticulum (SR) membranes that are opened upon binding of the second messenger, inositol triphosphate (IP3). These are intracellular Ca release channels that allow Ca to exit from intracellular stores, and consequently to increase the concentration of cytoplasmic Ca [5]. A second type of intracellular Ca release channel is the Ca - and ryanodine-sensitive channel that was originally characterized and isolated from cardiac and skeletal muscle [5-7] but appears to exist in many types of cells. It has become evident that IP3-gated channels and ryanodine-sensitive channels are structurally related but distinct proteins [8] that are present in many cell types [9]. While very interesting, time and space will not allow for further discussion of these channels. 

The first molecule, the Ca2+ channel, is required for coupling at the triad. Skeletal muscle contains higher concentrations of this L-type Ca2+ channel that can be accounted for on the basis of measured voltage-dependent Ca2+ influx because much of the Ca2+ channel protein in the T-tubular membrane does not actively gate calcium ion movement but, rather, acts as a voltage transducer that links depolarization of the T-tubular membrane to Ca2+ release through a receptor protein in the SR membrane. The ryanodine receptor mediates sarcoplasmic reticulum Ca2+ release. The bar-like structures that connect the terminal elements of the SR with the T-tubular membrane in the triad are formed by a large protein that is the principal pathway for Ca2+ release from the SR. This protein, which binds the... 

FIG. 1. Surface coupling in a portion of a smooth muscle cell from the chicken amnion. An element of junctional sarcoplasmic reticulum (SRj) separated by an 18 nm junctional gap between the plasma membrane and the SR is traversed by periodic bridging structures. 

The enzyme responsible for this topping-up ATP in active muscle is CK. CK is found in high concentration in muscle cells, both free within the sarcoplasm and also associated with membranes of mitochondria and the sarcoplasmic reticulum. Structurally, creatine kinase is a dimeric enzyme of B and/or M subunits, each of about 40 kDa. Three quaternary structure isoenzyme forms arise CK-MM, CK-BB and CK-MB. The predominant form in all muscles is CK-MM, but cardiac muscle also contains a significant amount of CK-MB and this isoenzyme can be used as a specific marker of myocardial damage (see Case Notes at the end of this chapter). 

Any dialogue on meat flavor development and deterioration requires a brief discussion of muscle structure. Muscle has a highly compact and complex multicellular structural organization (Figure 2). Individual muscle cells contain numerous mitochondria and nuclei. They also contain contractile elements as the bulk of their structure. While the sarcoplasm of muscle (the aqueous non-organellar component) is small compared to the cytoplasm of non-muscle cells, it does have a highly evolved system of membranes called the SR/L representing an acronym for sarcoplasmic reticulum/lysosomal membrane system (11). The SR/L surrounds each contractile element (Fig. 9-13 in 12 Fig. 7-10 in 13). The close proximity of the SR/L to the contractile proteins situates the proteins in a location that is optimal for their hydrolysis by lysosomal hydrolases (12, 13). 

Diagram of the structures involved in the stretch reflex arc. I is an inhibitory interneuron E indicates an excitatory presynaptic terminal la is a primary intrafusal afferent fiber Ca2+ denotes activator calcium stored in the sarcoplasmic reticulum of skeletal muscle RyR channels indicates the Ca2+ release channels. 

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

FIGURE 5-31 Structure of skeletal muscle, (a) Muscle fibers consist of single, elongated, multinucleated cells that arise from the fusion of many precursor cells. Within the fibers are many myofibrils (only six are shown here for simplicity) surrounded by the membranous sarcoplasmic reticulum. The organization of thick and thin filaments in the myofibril gives it a striated appearance. When muscle contracts, the I bands narrow and the Z disks come closer together, as seen in electron micrographs of (b) relaxed and (c) contracted muscle. 

Several uncertainties have complicated our understanding of the role of Ca2+ in signaling. What is the source of Ca2+ How much of it enters cells from the outside and how much is released from internal stores Where are the internal stores What other kinds of ion channels are present and what second messengers regulate them The sarcoplasmic reticulum of skeletal muscle and also membranes in many other cells contain ryanodine receptors as well as InsP3 receptors.282 293 Both of these receptors have similar structures and contain Ca2+ channels. However, the ryanodine receptors are activated by cyclic ADP ribose (cADPR),294/295 which was first discovered as a compound inducing the release of Ca2+ in sea urchin eggs.296 The 2-phospho derivative of cADPR may also have a similar function.297... 

A closer look at striated muscle fibers shows that they themselves are assemblies of fine, hairlike structures known as myofibrils (Fig. 1A, B). Myofibrils may be about 2 to 5 jxm in diameter, with cell organelles such as mitochondria and membranous systems called T-tubules and the sarcoplasmic reticulum (SR) sandwiched between them (Fig. 2B). 

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility (numbered structures). Site 1 is Na+/K+ ATPase, the sodium pump. Site 2 is the sodium/calcium exchanger. Site 3 is the voltage-gated calcium channel. Site 4 is a calcium transporter that pumps calcium into the sarcoplasmic reticulum (SR). Site 5 is a calcium channel in the membrane of the SR that is triggered to release stored calcium by activator calcium. Site 6 is the actin-troponin-tropomyosin complex at which activator calcium brings about the contractile interaction of actin and myosin.

The skeletal muscle ryanodine receptor, RyRl, controls the release of calcium, through a central channel, from the intracellular sarcoplasmic reticulum [34], The channel forms at the convergence of four identical protein subunits each of which contains two a-helices. One helix from each subunit is approximately 0.45 nm long and has a central kink. The overall effect is to give the channel a funnel-like entrance about 0.3 nm across leading to a central pore with a 0.15 nm diameter. The pore is defined by four further a-helices approximately 0.22 nm long, one from each subunit. Unfortunately the low resolution of the structure does not allow for detailed study of the filtering mechanism. 

Anatomical structure. The striated muscles of vertebrates consist of bundles of muscle fiber cells covered with connective tissue. A muscle fiber is composed of bundles of striated myofibrils surrounded by sarcoplasmic reticulum, mitochondria and other organelles. The unique structure of the striated myofibrils, composed of thin(actin)-filaments and thick(myosin)-filaments, is common to all striated muscles of vertebrates including fish (19,20). 

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