Ca2+ATPase

Tlie Na+/K+-ATPase belongs to the P-type ATPases, a family of more than 50 enzymes that also includes the Ca2+-ATPase of the sarcoplasmic reticulum or the gastric H+/K+-ATPase. P-Type ATPases have in common that during ion transport an aspartyl phos-phointermediate is formed by transfer of the y-phosphate group of ATP to the highly conserved sequence DKTGS/T [1]. 

Sarcoplasmic reticulum (SR) is a form of the smoothfaced endoplasmic reticulum (ER) in muscles. It functions as an intracellular Ca2+ store for muscle contraction. Ca2+ is energetically sequestered into the SR by Ca2+-pump/sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA) and released via Ca2+ release channels on stimuli (ryanodine receptor in striated muscles and inositol 1,4,5-trisphosphate receptor in most smooth muscles). Endoplasmic reticulum in non-muscle tissues also functions as an intracellular Ca2+ store. 

Butyrophenones Butyrylcholinesterase C2 Domain C Kinase C-reactive Protein Ca2+-ATPase Ca2+-binding Proteins Ca2+ Channel Ca2+ Channel Antagonists Ca2+ Channel Blockers... 

The structure and mechanism of the sarcoplasmic reticulum Ca2+-ATPase a bioinorganic perspective. E. M. Stephens andC. M. Grisham, Adv. Inorg. Biochem., 1982, 4, 263-288 (151). 

Ca2+-ATPase (348,349) Provides the means of pumping Ca2+ selectively across membranes (350,351)... 

Ca2+ pumps are needed for the removal of calcium from cells, as in the maintenance of low Ca2+ levels in resting muscle, in bone deposition, and in biomineralization. The Na+/Ca2+ exchanger and Ca2+-ATPase (a Ca2+/H+-exchanger) act in parallel to pump Ca2+ across membranes, the latter being considerably more effective than the former. X-ray structure determinations have been carried out both for Ca2+-ATPase and for its Ca2+-bound form (443). The latter contains two Ca2+ ions... 

Mahaney, J. E., Thomas, D. D. and Froehlich, J. P. The time-dependent distribution of phosphorylated intermediates in native sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle is not compatible with a linear kinetic model. Biochemistry 43 4400-4416, 2004. 

Toyoshima, C., Nomura, H. and Sugita, Y. Structural basis of ion pumping by Ca2+-ATPase of sarcoplasmic reticulum. FEBSLett. 555 106-110,2003. 

Two distinct mechanisms for controlling Ca at the plasma membrane are provided by a Ca2+-ATPase pump and a Na+/Ca2+ exchanger 380... 

The only known mechanism for Ca2+ accumulation by the endoplasmic reticulum is by means of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pumps 381... 

The plasma membrane Ca2+-ATPase pump effects outward transport of Ca2+ against a large electrochemical gradient for Ca2+. The mechanism of the pump involves its phosphorylation by ATP and the formation of a high-energy intermediate. This basic mechanism is similar for both the plasma membrane and ER pumps however, the structures of these distinct gene products are substantially different. As discussed below, the ER pump, sometimes called a sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) pump, is inhibited potently by certain natural and synthetic toxins that do not affect the plasma membrane pump. The plasma membrane pump, but not the SERCA pump, is controlled in part by Ca2+ calmodulin, allowing for rapid activation when cytoplasmic Ca2+ rises. 

FIGURE 22-3 Structures of compounds that inhibit sarcoendoplas-mic reticulum Ca2+-ATPase (SERCA) calcium pumps. 

Odermatt, A., Taschner, P. E., Khanna, V. K. etal. Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease. Nat. Genet.lA. 191-194,1996. 

As both fast and slow adaptation mechanisms are regulated by Ca2+, the stereocilia mechanisms that control the free concentration of this ion also play central roles in transduction. Entering Ca2+ is thought to be buffered very rapidly by the mobile buffers parvalbumin 3, calbindin, and calretinin [22,23]. Even before bound Ca2+ can diffuse out of stereocilia, it is pumped back out into the endo-lymph by isoform 2a of the plasma-membrane Ca2+-ATPase (PMCA2) [24,25] (see also Ca2+ transport in Ch. 5). 

B. L. and Noben-Trauth, K. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat. Genet. 19 390-394,1998. 

Kozel, P. J. et al. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. /. Biol. Chem. 273 18693-18696,1998. 

In biological systems, therefore, the behavior of Li+ is predicted to be similar to that of Na+ and K+ in some cases, and to that of Mg2+ and Ca2+ in others [12]. Indeed, research has demonstrated numerous systems in which one or more of these cations is normally intrinsically involved, including ion transport pathways and enzyme activities, in which Li+ has mimicked the actions of these cations, sometimes producing inhibitory or stimulatory effects. For example, Li+ can replace Na+ in the ATP-dependent system which controls the transport of Na+ through the endoplasmic reticulum Li+ inhibits the activity of some Mg2+-dependent enzymes in vitro, such as pyruvate kinase and inositol monophosphate phosphatase Li+ affects the activity of some Ca2+-dependent enzymes— it increases the levels of activated Ca2+-ATPase in human erythrocyte membranes ex vivo and inhibits tryptophan hydroxylase. 

P. Champeil, T. Menguy, C. Tribet, J-L. Popot, M. le Maire (2000) Interaction of amphipols with the sarcoplasmic Ca2+-ATPase. J. Biol. Chem., 275 18623-18637... 

Modulation of the SR Ca2+ ATPase by PLB perhaps provides the clearest evidence of the significance of the SR to smooth muscle Ca2+ homeostasis and contractility. It also offers some cautions since the effects of modulation of SR function were clearly dependent on the smooth muscle tissue studied. In summary, genetically altered mouse models provide a new approach for assessing the physiological significance of the SR to smooth muscle function in vivo. 

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