Detubulation effects on the action of zinc on frog skeletal muscle action potential

Abstract

Detubulation of the untreated fiber decreases the time constant of the action potential's foot (tauf) and increases the maximal rate of rise of the spike (Vmax). Zinc at all concentrations, and regardless of whether the fiber is intact or detubulated, increases tauf and decreases Vmax, and thus seems to decrease Na activation of the fiber. Detubulation was used principally to elucidate the localization and mechanism of the Zn2+-induced retardation of the falling phase of the frog sartorius fiber action potential, which evidently results from a general depression of delayed rectification. At 50 to 1000 mum, Zn2+ not only prolongs repolarization of intact fibers (measured by increase in t0.5, the half-time of the spike's fall), but also produces a marked hump early in this phase. Detubulation of zinc-free fibers reduces t0.5 to about 80% of its intact value, and under Zn2+ treatment t0.5 is increased but only to about 80% of that produced in the inus, detubulation decreases t0.5 in Zn2+-treated fibers not only to about 80% of that produced in the intact fiber, and the falling-phase hump is completely obliterated. Thus, detubulation decreases t0.5 in Zn2+-treated fibers not only by generally eliminating T-tubular participation in action potential generation, but also by subtracting a Zn2+-induced retardation of tubular delayed rectification. Tubular delayed rectification must therefore be an intrinsic feature of normal excitation. These results are further analyzed by means of (i) Stanfield's findings about retardation of delayed rectification by Zn2+ and (ii) Adrian-Peachey's theory of T-tubule participation in action potential generation, which suggests that the Zn2+-evoked repolarization hump signals onset of Zn2+-altered active participation of T-tubules in determining the spike's shape.

Zinc inhibition of potassium efflux in depolarized frog muscle and its modification by external hydrogen ions and diethylpyrocarbonate treatment

“…External Zn 2+ up to about 0.1 mM produces twitch potentiation (Isaacson & Sandow, 1963;Sandow, Taylor, Isaacson & Seguin, 1964) and a parallel prolongation of the falling phase of the action potential (Mashima & Washio, 1964;Sandow et al, 1964;Edman & Grieve, 1966) principally caused by a slowing of potassium currents through the delayed rectifier (Stanfield, 1975). There is little change in the overshoot or maximum rate of rise of the action potential (Mashima & Washio, 1964;Sandow et al, 1964;Sandow & Pagala, 1978).…”

“…For [Zn2+]o between 0.1 and !.0 raM, the action potential duration continues to increase (Mashima & Washio, 1964;Taylor, Preiser & Sandow, 1972), the maximum rate of depolarization and overshoot are reduced (Taylor et al, 1972;Sandow & Pagala, 1978), and there is a decrease in membrane chloride conductance with little change in the resting potassium conductance (Mashima & Washio, 1964;Hutter & Warner, 1967b;Stanfield, 1970). The resting membrane potassium conductance in frog skeletal muscle fibers is generally ascribed to the inward potassium rectifier (Katz, 1949;Hodgkin & Horowicz, 1959;Adrian & Freygang, 1962).…”