The action of caffeine on the activation of the contractile mechanism in striated muscle fibres

Abstract

The effect of caffeine on the initiation of isometric tension in isolated twitch muscle fibers of the frog was recorded with a mechano-electrical transducer. In Ringer solution and in solutions containing 95 m[image]-K2SO4, caffeine (6-10 m[image]) caused reversible contractores. Tension of maximal K contractures was reached with 1/2 time of 2-4 sec. Caffeine caused a shift to lower K concentrations of the S-shaped curve which relates peak tension to log. [K]o or membrane potential. In subthreshold concentrations of caffeine (1.5 m[image]) the K concentration at which 1/2 of maximal tension was reached shifted from 30 to 16 m[image]-K ([long dash]39 to[long dash]53 mV). In the "steady state" the ability of fibers to develop tension is related to log. [K]o or membrane potential by an S-shaped curve whose 1/2 value shifted from 28 to 45 m[image]-K ([long dash]41 to[long dash]20 mV) when 1.5 mM caffeine was applied. Fibers were most sensitive to caffeine at membrane potentials between[long dash]50 and[long dash]20 mV. The mechanical activity caused by caffeine was stabilized by an increase in [Ca]o or [Mg]o resembling the stabilizing action of these ions on K contractures or on the Na permeability of excitable membranes. Tetracaine in low concentrations (0.04-0.1 m[image]) increased the threshold for mechanical activation and shortened the plateau of K contractures. Higher concentrations (1-2 m[image]) suppressed mechanical activity completely. Tetracaine, 0.04 m[image], was sufficient to suppress tension caused by a 100 times stronger concentration of caffeine. With higher concentrations of caffeine the inhibitory action of tetracaine could be reversed.