Parvalbumins and muscle relaxation: a computer simulation study

Abstract

The distribution of Ca²⁺ and Mg²⁺ among the ‘regulatory’ cation binding sites of troponin (T-sites) and the strong, Ca²⁺-Mg²⁺ binding sites of troponin and parvalbumins (P-sites) in the sarcoplasm of a muscle was calculated. At rest, 60% of the T-sites were metal free, while 92% of the P-sites were loaded with Mg²⁺. In response to a Ca²⁺ pulse, troponin-calcium (T-Ca) complexes were rapidly formed, while the binding of Ca²⁺ to P-sites was limited by the slow rate of dissociation of the parvalbumin-magnesium (P-Mg) complexes. Muscle activation was not prevented by a high content of parvalbumins. Parvalbumin and the sarcoplasmic reticulum (SR) pump were complementary relaxing factors that removed Ca²⁺ from the cytosol and from the T-sites. Parvalbumins dominated the first part of relaxation, while the action of the SR was essential to ensure the return to a very low level of free Ca²⁺ ion and of T-Ca. After relaxation, a large fraction of the Ca²⁺ pulse was still bound to parvalbumins and returned slowly to the SR during the recovery. When the SR activity was reduced, the presence of parvalbumins preserved a fast rate of relaxation, at least for a few contractions. This may have a high adaptive value in cold-blooded animals.