Skip to content
Login Register

#Ca2+

2 public questions tagged with this topic.

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
Cytoskeleton

During muscle contraction, what happens when Ca2+ binds to troponin-C?

Skeletal muscle contraction controlled by steric blocking mechanism where tropomyosin position on thin filament determines myosin access. Relaxed state low cytoplasmic calcium 100 nanomolar tropomyosin coiled coil dimer spanning seven actin monomers lies on outer edge of actin blocking myosin binding sites, stabilized by troponin I inhibitory peptide binding actin. Troponin complex anchored via TnT 30 kilodalton binding C terminal tropomyosin, TnI 21 kilodalton inhibitory, TnC 18 kilodalton calcium sensor with two N terminal regulatory EF hands. Action potential opening voltage gated calcium channel DHPR triggers ryanodine receptor RyR1 releasing calcium from sarcoplasmic reticulum raising concentration to 10 micromolar. Calcium occupying N lobe EF hands of TnC induces opening hydrophobic pocket recruiting C terminal switch peptide of TnI pulling it off actin. Concomitant azimuthal movement tropomyosin about 25 degrees toward inner groove documented by cryo EM uncovers myosin binding sites permitting cross bridge formation power strokes and contraction. Filaments do not depolymerize during activation.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17: Troponin C Calcium Binding and Tropomyosin Shift.

View Details