Skeletal muscle fibers when depolarized to a potential at which contraction is activated show a small, transient outward current which can be attributed to movement or rearrangement of charges confined to the membrane. The characteristics of this voltage dependent charge movement suggest that it may play a role in activating contraction. Experiments are planned to compare some of the properties of these charge movements with those of Ca ion release to see whether, in fact, the two processes are related. If so, we shall try to find out what the relationship is. Indicator dyes will be used to obtain estimates of intracellular pH and Mg ions in muscle fibers and to see whether dyes behave differently inside muscle fibers, because of binding, than they do in cuvettes. An attempt will be made to synthesize new and better Ca ion indicator dyes. These need to form complexes with Ca ions of simple stoichiometry, to be insensitive to changes in pH and Mg, to be fast, and to not bind to cellular constituents. A search will be made to find a dye that has a high affinity for Ca ions so that most of the Ca ions released during a twitch would be bound to the dye. Optical signals from this dye would be used to study the time course of Ca ion release rather than the time course of ionized Ca ions.
