Topochemical Factors in Potentiation of Contraction by Heavy Metal Cations

Abstract

In addition to the previously studied Zn ~+, low concentrations (about 0.5 mM) of Be g+, Ba ~+, Cd 2+, Ni ~+, Cu 2+, Pt 4+, and, outstandingly, 0.5 /~ of ~+ UOa , potentiate the twitch of frog sartorius and toe muscles by prolonging the active state of contraction. The degree of potentiation is a roughly S-shaped function of p(metal2+), suggesting that each metal binds to a ligand of the muscle fiber, representative apparent affinity constants being: UO~ +, 5 X 106; Zn ~'+, 2.8 X 105; and Cd 2+, 2 X 104. UO~ + potentiation effects are rapidly reversed by PO4, and Zn 2+ and Cd 2+ effects by EDTA, PO4, and cysteine. The rapidity of these reversals by the nonpenetrating EDTA and PO~, and the fact that heavy metal ions evidently potentiate by prolonging the action potential, indicate that the metal potentiators exert their primary action at readily accessible (i.e. plasma and T tubular) membrane sites. The relatively slow kinetics of development of potentiation, and the even slower reversal of it in pure Ringer's solution, indicate that the metal ions are bound to connective tissue, as well as to muscle fibers. The binding effects at the readily accessible membrane sites evidently impairs delayed rectification and thus modifies the action potential and excitation-contraction coupling so as to cause potentiation. SH is excluded, and PO4 and imidazole are possibilities, as the membrane ligand binding the potentiating metal ions.Contraction of skeletal muscle is potentiated by many chemically diverse substances which include a group of divalent heavy metals, exemplified especially by zinc ; for general review of potentiation, see . All these agents typically augment the isometric twitch by as much as 2 to 3 times, but do not significantly change the peak tetanus tension (for certain exceptions see Brust, 1965). In our previous work we attempted to locate the site of action of Zn by using techniques which involved the kinetics of development and reversal of twitch potentiation and located the primary site of action of the anionic potentiators NO~-and I -at either the plasma, or T tubular, membrane (Kahn and Sandow, 1950, 1955;Hill

Effects of twitch potentiators and repetitive stimulation on arsenazo III Ca-transients in Xenopus skeletal muscle fibers.

“…The AZ III signal was also prolonged so that T2 and T3 were 6.4 and 23 msec, whereas Tl was little changed. It was reported that Zn action potential or twitch tension developed slowly and it took 1 min for the Zn action to attain the maximum when examined for a single fiber (STANFIELD, 1973), or 7 min examined for the toe muscle (SANDOW and IsAACSON, 1966). In the present study, the muscle preparation was a single layer of a few fibers and the solution was not exchanged rapidly.…”

Effects of sulphydryl inhibitors on frog sartorius muscle: N‐ethylmaleimide

“…Sandow & Isaacson (1966) also reported a contractile effect of NEM. In the present experiments, however, the contractile effect was seen infrequently and was of very variable amplitude.…”

The influence of stimulus parameters on contractions of isolated frog muscle fibres

“…Also, the shoulder which quite often appears on the falling phase of the twitch (Text- fig. 1 D, E In like manner, when a curarized whole muscle is stimulated with transverse pulses, prolonging the stimulus from 0-2 to 10 msec decreases the twitch amplitude (Kelly et al 1964;Sandow & Isaacson, 1966;Close & Hoh, 1968). But when curare is absent the force of the contraction elicited is greatly increased as the stimulus duration is prolonged (Kelly et al 1964).…”