Nickel Substitution for Calcium in Excitation-Contraction Coupling of Skeletal Muscle

In 1962 Frank (22) reported that the addition of any one of a number of divalent cations, including Ni, to a Ca-free Ringer solution prevented the rapid loss of contractility seen in the absence of external Ca. To investigate further the Ni-Ca substitution, studies were made of (45)Ca and (63)Ni exchange during contraction and at rest using frog striated muscle. In contrast to (45)Ca, it was found that there is no increase of (63)Ni uptake associated with a K contracture of the sartorius muscle. The rates of loss of (63)Ni and (45)Ca from resting toe muscles previously bathed in the respective radioisotopes are not significantly different. Resting and action potentials, after 1 hr in a Ringer solution with Ni replacing Ca, closely resemble these potentials in normal Ca-Ringer's solution. Studies on the syneresis of isolated myofibrils indicate that Ni cannot replace Ca in activating this reaction. It is suggested that Ca is required for at least two steps in E-C coupling: one is the spread of excitation at the sarcolemma and transverse tubular system; the second is the activation of actomyosin ATPase. Conceivably Ni can substitute for Ca in the former but not in the latter.