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

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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.