Intracellular EDTA mimics parvalbumin in the promotion of skeletal muscle relaxation

Parvalbumin (PA) is an intracellular Ca²⁺-binding protein found in some muscle and nerves. Its ability to bind Ca²⁺ and facilitate skeletal muscle relaxation is limited by its Mg²⁺ off-rate. EDTA serves as an 'artificial' PA in that it exhibited similar rate constants for Mg²⁺ (3 s^{- 1}) and Ca²⁺ (0.7 s^-1) dissociation at 10°C. When introduced into frog skeletal muscle, EDTA increased the relaxation rate by ~2.7-fold, and with increasing tetanus duration, EDTA lost its ability to contribute to relaxation (and Ca²⁺ sequestration) at its Mg²⁺ off-rate. Intracellular EDTA recovered its ability to contribute to muscle relaxation and Ca²⁺ sequestration at its Ca²⁺ off-rate. Like PA, EDTA's contribution to muscle relaxation and Ca²⁺ sequestration was more clearly observed when the SR Ca- ATPase was inhibited. Introduction of EDTA into rat soleus muscle, which has low [PA], increased the relaxation rate in a manner that was analogous to the way in which PA facilitates relaxation of frog skeletal muscle. Thus intracellular EDTA serves as an effective mimic of PA, and its use should aid in our understanding of PA's function in muscle and nerve.