Magnesium and the regulation of muscle contraction

Fed Proc. 1981 Oct;40(12):2653-6.


There are a variety of Ca2+ binding sites in muscle (e.g., troponin, parvalbumin, myosin, and calmodulin) that may play a role in the regulation of muscle contraction an other enzymatic processes. since most of these proteins also bind Mg2+, it is important to consider the effect that the high free Mg2+ concentration (mM) found in muscle has on the Ca2+ binding properties of these sites. The major effect of Mg2+ is to greatly reduce the rate of Ca2+ binding to the sites that bind Mg2+ and Ca2+ competitively (Ca2+-Mg2+-type sites found in troponin, parvalbumin, and myosin, which would be essentially saturated with Mg2+ in a relaxed muscle) due to the slow dissociation of bound Mg2+. Thus during a transient increase in [Ca2+] similar to that which would occur during muscle activation, these sites would bind very little Ca2+ and, consequently, could not play a regulatory role. Even if Ca2+ were able to bind to these sites during muscle activation (e.g., if the free Mg2+ in muscle is lower than presumed), the dissociation of Ca2+ from these sites would be quite slow due to their very slow off rates for Ca2+, again making these sites unsuitable for participating in a rapid Ca2+-induced switching mechanisms. In contrast, the Ca2+-specific-type (regulatory) sites found in troponin and calmodulin do not have these restraints. The rate of Ca2+ binding to these sites is not affected by Mg2+ and the off rate of Ca2+ from these sites is very rapid due to their lower Ca2+ affinity. Thus, these sites are able to respond to rapid Ca2+ transients, an essential feature for any Ca2+ binding site that plays a regulator role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Binding, Competitive
  • Calcium / physiology
  • Calmodulin / physiology
  • Enzyme Activation
  • Humans
  • Magnesium / physiology*
  • Muscle Contraction*
  • Myosins / physiology
  • Parvalbumins / physiology
  • Troponin / physiology


  • Calmodulin
  • Parvalbumins
  • Troponin
  • Myosins
  • Magnesium
  • Calcium