Practice question

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.