Ca2 pump

Intracellular Ca2+-levels are controlled by release into, and removal from, the cytoplasm (Fig. 1). Ca2+-pumps in the plasma membrane and endoplasmic reticulum (ER the Ca2+-store in a cell) keep cytoplasmic Ca2+-levels low (about 0.1 pmol/L in resting cells) and generate a 10,000-fold concentration gradient across membranes (because extracellular Ca2+ is in the millimolar range). Upon stimulation, Ca2+ enters the cytosol of the cell via Ca2+-channels (plasma membrane) or via Ca2+-channels in the ER, leading to the activation of a great variety of Ca2+-dependent processes in the cell. 

Ca2+-pumps. After entering the cell, Ca2+ is reversibly complexed to specific Ca2+-binding proteins that fiilfil multiple functions, including Ca2+-buffering and transport, activation of enzymes, regulation of contraction,... 

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. 

In striated muscles, SR is well developed to surround the myofibrils and is divided into two parts, the terminal cisternae (TC) and longitudinal tubules (LT). TC forms triad (skeletal muscle) or dyad (heart) structure with transverse tubules. The ryanodine receptor is located only in the TC, whereas the Ca2+ pump/SERCA is densely packed in both TC and LT. 

Calcium is pumped out of the cytosol by Ca2+ pumps in the plasma membrane, endoplasmic reticulum, or mitochondria. 

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... 

ATP-dependent Ca2+ pumps and Na+,Ca2+ antiporters act in concert to maintain a low concentration of free cytosolic Ca2+ 79 The uniquely high resolution structural data available for the SERCAla Ca2+ pump illuminates the structure of all P-type transporters 81 P-type copper transporters are important for neural function 82... 

Genetic evidence supports the importance of coordinated expression and distributions of a2 or a3 Na+/K+ pump isoforms with the Na+/Ca2+ exchanger (NCX) and Ca2+ pumps to function in excitable and contractile cells deletion of one copy of the a2 Na+/K+ pump gene in mice leads to increased contractile force in cardiac and skeletal muscle while deletion of one copy of the al gene leads to reduction of contractile force [25]. In rat optic nerve astrocytes, deletion of the a2 gene or ouabain treatment of cells expressing a2 leads to increased capacitative calcium entrance responses, which reflect a decreased ability to rapidly remove cytosolic Ca2+ [26]. 

PMCA plasma-membrane Ca2+ pump SCIP suppressed cyclic AMP-inducible POU domain protein... 

Caroni P, Carafoli E (1981) Regulation of Ca2+ -pumping ATPase of heart sarcolemma by a phosphorylation-dephosphorylation process. J Biol Chem 256 3262-3270... 

FIG. 2. The capacitative Ca2+ entry complex. The SR, with its resident Ca2+ pump (SERCA) and InsP3 receptors the plasma membrane, with the channels fl(-RAc) regulated by empty stores and mitochondria are all proposed to be intimately associated in this capacitative Ca2+ entry complex. Inevitably, as Ca2+ enters via Icrao I nslb receptors and SERCA will be transiently exposed to very high [Ca2+]c the implications are discussed in the text. 

Ca2+ homeostasis that results from graded Ca2+ influx through voltage-dependent Ca2+ channels (Fleischmann et al 1994) and spontaneous intracellular Ca2+ release through ryanodine receptors. Thus the myocyte integrates numerous Ca2+ inputs and the concentration of cytosolic free Ca2+ ([Ca2+]j) at any given time is the net result of the activity of these Ca2+ channels, as well as that of Ca2+ pumps and exchangers that remove Ca2+ ions from the cytosol. 

Blaustein Some areas empty and others fill when we put on CPA. This means that there are some SERCA Ca2+ pumps that are insensitive to CPA. A number of studies have demonstrated that there are some SERCA pumps that are insensitive. If you dump Ca2+ out of some regions and other Ca2+ pumps are still working, you are going to fill those regions. 

The SERCA2 homozygous null mouse (—/—) is lethal, but the heterozygous mouse has been useful in assessing the cardiovascular effects of a reduction of SERCA2 protein. Significant alterations in cardiac function were observed (Periasamy et al 1999). However, neither mouse aorta nor portal vein contractility were affected (Weber 1999). We verified that the SERCA protein was indeed reduced so the negative results may indicate that there is a substantial reserve of Ca2+ pump activity. 

Eggermont JA, Wuytack F, Verbist J, Casteels R 1990 Expression of endoplasmic-reticulum Ca2+-pump isoforms and of phospholamban in pig smooth-muscle tissues. Biochem J... 

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