Skip to content
Login Register

#sarcoplasmic reticulum

8 public questions tagged with this topic.

Membrane Transportation

Which ion is transported into the sarcoplasmic reticulum (SR) by SERCA?

Muscle contraction cycle requires rapid increase and decrease of cytosolic free calcium. At rest calcium about 100 nanomolar maintained by pumps and buffering proteins. Depolarization opens Cav1.1 dihydropyridine receptors mechanically coupled to RyR1 ryanodine receptors in skeletal muscle releasing calcium stored at millimolar total bound to calsequestrin in sarcoplasmic reticulum terminal cisternae, raising cytosolic calcium to ten micromolar activating troponin and cross bridge formation. For relaxation SERCA pump, sarco endoplasmic reticulum Ca2+ ATPase, abundantly expressed up to 70 percent of SR protein, actively resequesters calcium. It is 110 kilodalton P-type ATPase with ten transmembrane helices, two calcium binding sites high affinity cytosolic facing, ATP driven phosphorylation at Asp351 forming E1P Ca2+ occluded, transition to E2P low affinity lumenal releasing, two calcium per ATP transported against about 10,000 fold gradient. Thapsigargin irreversible inhibition depletes SR stores triggering ER stress. Plasma membrane Ca2+ ATPase PMCA and Na+/Ca2+ exchanger NCX supplement, but bulk reuptake into reticular store mediated by SERCA.

Ref: Toyoshima et al., Nature, SERCA Ca2+ ATPase Structure and Sarcoplasmic Reticulum Calcium Transport.

View Details
Cytoskeleton

Which ion plays a crucial role in triggering muscle contraction?

Triggering of all muscle types converges on transient elevation of calcium as intracellular messenger linking excitation to contraction coupling electrical and mechanical events effectively. Resting cytosolic calcium held near 100 nanomolar by SERCA pumps actively sequestering calcium in sarcoplasmic endoplasmic reticulum lumen. Action potential propagating along sarcolemma and T tubules activates voltage gated L type channels physically coupled to ryanodine receptors in striated muscle causing explosive calcium release raising concentration to 10 micromolar in microdomains near thin filaments. Calcium binds to EF hand motifs: troponin C in skeletal cardiac exposing myosin binding sites on actin via tropomyosin movement and calmodulin in smooth muscle activating myosin light chain kinase phosphorylating regulatory light chain. Sodium influx initiates excitation but does not directly activate contractile proteins potassium and magnesium maintain electrochemical gradients and serve as ATP Mg cofactor. Rapid pump mediated calcium reuptake ends signal making calcium ideally suited for rapid reversible control of force and speed of contraction.

Ref: Alberts et al., Molecular Biology of the Cell, Chapter 15 – Calcium ion as crucial trigger for muscle contraction.

View Details
Cytoskeleton

In skeletal muscle contraction, which protein regulates Ca2+ reuptake into the sarcoplasmic reticulum?

Relaxation requires rapid calcium clearance to restore resting state permitting cross bridge detachment and tropomyosin return to blocking. Sarcoplasmic reticulum calcium ATPase SERCA, family of P type ATPases with ten transmembrane helices and three cytoplasmic domains N P A, couples ATP hydrolysis to transport of two calcium ions per cycle from cytosol to SR lumen against concentration gradient 10,000 fold. In skeletal fast twitch SERCA1a constitutes 60 percent SR protein, in cardiac SERCA2a regulated by phospholamban PLN small inhibitor that reduces calcium affinity when dephosphorylated, phosphorylation by PKA relieves inhibition accelerating relaxation during sympathetic stimulation. Sarcolipin SNL similar regulator in skeletal muscle. Cytosolic calcium drops from peak 10 micromolar to 100 nanomolar within 20 milliseconds enabling troponin to revert. Myosin generates force not calcium reuptake, calmodulin sensor activating MLCK, tropomyosin blocks access. SERCA inhibition by thapsigargin or cyclopiazonic acid depletes SR stores, raises cytosol, causing contracture and ER stress, demonstrating central role for Ca2+ ATPase in reuptake and muscle relaxation.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17: SERCA Ca2+-ATPase and Muscle Relaxation.

View Details