Confirmatory Analysis of the "Lost" Italian Varnish

Abstract

An hypothesis was set up with the postulate that the rate of transport of K from within to outside nerve fibers (e.g., under the cathode on "make") is a controlling factor in stimulation. On this basis, cocaine and related compds. would act by decreasing membrane permeability to K. Expts. were carried out to test such changes in the sciatic nerve and sartorius muscle of Rana pipiens. Permeability of muscle to anions as well as K causes this tissue to swell in solns. in which, Na is replaced by K; the rate of wt. increase in such media is a measure of relative permeabilities. When half the Na in Ringer''s soln. is replaced, the wt. increase is markedly reduced by 0.2% cocaine, a concn. which does not abolish response to electrical stimulation, and water movement is hardly affected. Cocaine reduces KC1 penetrability. KC1 diffusion was incomplete after 2 hrs.; however, the max. lowering of potential, produced at the tibial end by Ringer''s soln. with 1/5 of its Na replaced with K, was reached in 10-20 min. This was not a Donnan equilibrium potential drop. Rather, the conditions justify the application of the equation for a diffusion potential. Short-circuiting by the extracellular space and swelling of fibers limit the significance of the absolute potential changes obtained. However, it is predicted from the equation that if the mobility of K relative to Cl is reduced, the effectiveness of K in lowering potential will be correspondingly affected. The action of cocaine was typical in all expts. and supports the view that K penetrability is reduced by the anesthetic. For frog nerve, the rise of resting potential in 5% CO2-O2 and its decline during anoxia result from the uptake and release of K by the fibers, the changes in K conc. of the extracellular spaces being the immediate chief cause of the potential changes. Reduced permeability to K is thus indicated by a decrease in the potential changes in both cases. The expts. support the view that certain concs. of cocaine reduce the permeability of frog nerve and muscle to K.