SERCA calcium-ATPase

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. 

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

The deterministic dynamics of this cluster model has been investigated in [32, 33]. In addition to IP3 mediated Ca liberation, we considered sarco-endoplasmic reticulum calcium ATPase (SERCA) pumps, which transport Ca from the cytosol to the ER, and a leak flux. The stationary Ca concentration profile that results from these three fluxes is... 

O Ruthenium Nitrogen Oxygen Cartxxi Figure 15 Proposed nitric oxide release and vasodilation mechanism induced by the [Ru(tpy)(NH NHq)NO] complex. The colored (different gray shades in the print version) circles represent atoms in the chemical structure. The hydrogen atom has been omitted in the structure. Legend sGC, soluble guanylyl cyclase GK, G Kinase Protein SERCA, sarco/endoplasmic reticulum calcium-ATPase Ca, calcium K, potassium [Ca o cytosolic calcium concentration. 

Researchers have studied whether acyl-chain order could be responsible for the preferred sterol interaction with SMs. Acyl-chain order was deduced from diphenylhexatriene anisotropy and from the deuterium order parameter obtained by H-NMR on bilayers made from either 14 0/14 0(d27)-PC, or 14 0(d27)-SM7 Some researcher analyzed the ground and excited states of phospholamban (PLN), a membrane protein that regulates sarcoplasmic reticulum (SR) calcium ATPase (SERCA), in dilferent membrane mimetic environments. Gustavsson et al. have previously proposed that the conformational equilibrium of PLN are central to SERCA regulation. They have now shown that these equilibrium detected in micelles and bicelles are also present in native sarcoplasmic reticulum lipid membranes as probed by MAS solid-state NMR. ... 

SERCA Sarco/endoplasmic reticulum calcium ATPase... 

Conformational dynamics are often inferred and quantified from the motional averaging of the NMR parameters. Here De Simone et al. have employed oriented solid-state NMR data, such as dipolar couplings and chemical shift anisotropy measured in lipid bicelles, to refine the conformational ensemble of these proteins in lipid membranes. They specifically investigated calcium ATPase SERCA. ... 

Phospholamban (PLB or PLN) is a single-pass, 52-residue integral membrane protein that regulates myocardial contractility by direct physical interaction with sarco(endo)plasmic reticulum Ca-ATPase (SERCA), a 110-kDa enzyme that maintains calcium homeostasis in the sarcoplasmic... 

Some sarco(endo)plasmic reticulum (SR) Ca +-ATPases (SERCA) are P-type ATPases that play a major role in muscle contraction-relaxation cycles and are responsible for transporting calcium into the lumen of the sarcoplasmic reticulum. Some definitions are useful in the discussion of Ca +-ATPases ... 

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility. Na+,K+ ATPase, the sodium pump, is the site of action of cardiac glycosides. NCX is the sodium, calcium exchanger. Cav-L is the voltage-gated, L-type calcium channel. SERCA (sarcoplasmic...

Cardiac glycosides increase contraction of the cardiac sarcomere by increasing the free calcium concentration in the vicinity of the contractile proteins during systole. The increase in calcium concentration is the result of a two-step process first, an increase of intracellular sodium concentration because of Na+,K+ ATPase inhibition and second, a relative reduction of calcium expulsion from the cell by the sodium-calcium exchanger (NCX in Figure 13-1) caused by the increase in intracellular sodium. The increased cytoplasmic calcium is sequestered by SERCA in the SR for later release. Other mechanisms have been proposed but are not well supported. 

Cyclopiazonic acid is a potent inhibitor of calcium uptake and acts as a selective inhibitor of the sarco-endoplasmic reticulum Ca2+ATPases (SERCAs) [53], it induces charge alteration in plasma membranes and mitochondria and it can function as an antioxidant [54]. 

The cytosolic concentration of free Ca2+ is generally at or below 100 mi, far lower than that in the surrounding medium, whether pond water or blood plasma. The ubiquitous occurrence of inorganic phosphates (Pj and I l ,) at millimolar concentrations in the cytosol necessitates a low cytosolic Ca2+ concentration, because inorganic phosphate combines with calcium to form relatively insoluble calcium phosphates. Calcium ions are pumped out of the cytosol by a P-type ATPase, the plasma membrane Ca2+ pump. Another P-type Ca2+ pump in the endoplasmic reticulum moves Ca2+ into the ER lumen, a compartment separate from the cytosol. In myocytes, Ca2+ is normally sequestered in a specialized form of endoplasmic reticulum called the sarcoplasmic reticulum. The sarcoplasmic and endoplasmic reticulum calcium (SERCA) pumps are closely related in structure and mechanism, and both are inhibited by the tumor-promoting agent thapsigargin, which does not affect the plasma membrane Ca2+ pump. 

In muscle cells, the contraction is induced by Ca2+ release from the sarcoplasmic reticulum, as a result of membrane depolarization and activation of RyRl receptors located at the surface of the SR. The subsequent transport of cytoplasmic Ca2+ back into the lumen of the sarcoplasmic reticulum restores low resting calcium levels and allows muscle relaxation. In fast-twitch skeletal muscle fibers, Ca2+ uptake is mediated by the sarco(endo)plasmic reticulum Ca2+ ATPase SERCA1 which represents more than 99% of SERCA isoforms in these muscle fibers. 

Calcium pumps, also termed Ca +-ATPase, are calcium channels that transport calcium from the low concentration cytoplasm to the high concentration extracellular space or ER/SR lumenal side using the energy of ATP hydrolysis. Based on their locations, calcium pumps are classified into two groups, plasma membrane Ca +-ATPase (PMCA) and sarcoplasmic reticulum Ca +-ATPase (SERCA). " Four basic isoforms of PMCA (PMCAl 4) have been identified and the other PMCA isoforms are the alternative splicing products of the basic isoforms. PMCAl and 4 are ubiquitously expressed in different tissues and PMCA2 and 3 are expressed in nerve cells. Three basic isoforms of SERCA pump and several sphcing variants have also been identified. ... 

SERCA Sarco/endoplasmic reticulum Ca + as in SERCA-ATPase, a calcium pump... 

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