Calcium-activated sarcoplasmic

Gitelzon, G. I., Tugai, V. A., and Zakharchenko, A. N. (1990). Production of obelin, a calcium-activated photoprotein, from Obelia longissima and its application for registration of the calcium efflux from the fragmented sarcoplasmic reticulum of skeletal muscles. Ukr. Biokhim. Zh. 62 69-76. 

It has been postulated that 2-PAM exerts its cardiac action in rabbit atria through its alteration of calcium metabolism. The relaxation phase of skeletal muscle contraction seems to be directly affected by the sarcoplasmic reticulum because of its ability to sequester calcium actively.29,46 a similar role has been suggested for the sarcoplasmic reticulum in cardiac muscle. 6,83 The onset of muscle contraction takes place when calcium reaches a crit-cal concentration. This contraction is later reduced by the increased calcium-sequestering activity of the sarcoplasmic reticulum. Thus, 2-PAM can affect this process by decreasing the rate of calcium uptake by the sarcoplasmic reticulum, which results in increasing the time required to reduce the calcium concentration enough to allow relaxation to take place. This was demonstrated by the Increase in the relaxation phase. It was suggested that this... 

Calcium-activated ATPase of the sarcoplasmic reticulum membranes... 

Chapter 7. Calcium-activated ATPase of the sarcoplasmic reticulum membranes, by W. Hasselbach... 

It seems probable that the activation of an ATP-ase by Ca ions indicates that a transfer mechanism for Ca exists in the membranes of the ghosts. This transfer would be directed outwards. The efflux of calcium from ghosts is greater if ATP is added to the system. Moreover, salyrgan inhibits this phenomenon and the effective concentration is within the range of that found to inhibit the ATP-ase activity. 2,6-Dichlorophenol-indophenol. an inhibitor of the ATP-ase activated by Ca ions, prevents the accumulation of calcium in sarcoplasmic vesicles. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

Sarcoplasmic calcium ATPase this enzyme utilizes the energy gained from hydrolysis of ATP to pump calcium from the cytosol into the stores of the sarcoplasmic reticulum. Its activity is negatively regulated by the closely associated protein phospholamban, and this inhibition is relieved upon phosphorylation of phospholamban by protein kinase A (PKA). 

Smooth muscle sarcoplasm contains a myosin light chain kinase that is calcium-dependent. The Ca activation of myosin fight chain kinase requires binding of calmodulin-4Ca to its kinase subunit (Figure 49-14). 

Calcium ions are actively pumped back into the extracellular fluid as well as the sarcoplasmic reticulum. When the concentration of calcium falls below... 

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

Increases in the concentration of calcium in the cytosol provides a signal that can initiate muscle contraction, vision, and other signaling pathways. The response depends on the cell type. In muscle, a transient rise in the cytosolic calcium levels (from opening calcium channels in the sarcoplasmic reticulum) causes contraction. This signaling in contraction is a direct consequence of electrical activation of the voltage-gated channel. 

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... 

Taggart MJ, Wray S 1998 Contribution of sarcoplasmic reticular calcium to smooth muscle contractile activation gestational dependence in isolated rat uterus. J Physiol 511 133—144... 

Creed KE, Ishikawa S, Ito Y 1983 Electrical and mechanical activity recorded from rabbit urinary bladder in response to nerve stimulation. J Physiol 338 149-164 Cui J, Cox DH, Aldrich RW 1997 Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels. J Gen Physiol 109 647-673 Fabiato A 1983 Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245 0-04... 

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

---