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

Abstract

1. The effect of caffeine on the initiation of isometric tension in isolated twitch muscle fibres of the frog was recorded with a mechano-electrical transducer.2. In Ringer solution as well as in solutions containing 95 mM-K(2)SO(4), caffeine (6-10 mM) caused reversible contractures. Tension of maximal potassium contractures was reached with a half-time of 2-4 sec.3. Caffeine caused a shift to lower potassium concentrations of the S-shaped curve which relates peak tension to log. [K](o) or membrane potential. In subthreshold concentrations of caffeine (1.5 mM) the potassium concentration at which half of maximal tension was reached shifted from 30 to 16 mM-K (-39 to -53 mV).4. In the ;steady state' the ability of fibres to develop tension is related to log. [K](o) or membrane potential by an S-shaped curve whose half value shifted from 28 to 45 mM-K (-41 to -29 mV) when 1.5 mM caffeine was applied.5. Fibres were most sensitive to caffeine at membrane potentials between -50 and -20 mV.6. 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 potassium contractures or on the sodium permeability of excitable membranes.7. Tetracaine in low concentrations (0.04-0.1 mM) increased the threshold for mechanical activation and shortened the plateau of potassium contractures. Higher concentrations (1-2 mM) suppressed mechanical activity completely.8. Tetracaine, 0.04 mM, 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.9. Fibres which were immersed in subthreshold concentrations of caffeine either in Ringer solution or in a solution with 95 mM-K(2)SO(4) developed a strong contracture after a sudden drop in temperature from 20 to 1-3 degrees C.10. The fast activation of the whole cross-section of the muscle fibre caused by caffeine and its dependence on membrane potential, tetracaine and external alkali earth ions favours the idea that the drug acts at some part of the sarcotubular system which is easily accessible for external ions and drugs and in close connextion with the surface membrane.

Functional expression of the calcium release channel from skeletal muscle ryanodine receptor cDNA

“…The pharmacological activation of the calcium release mechanism is similar to that observed in intact skeletal muscle fibres [19], as witnessed by the changes in [Cali induced by caffeine and ryanodine. As in muscle cells, caffeine causes a prompt increase in [Cali that rapidly fades as the drug is removed.…”

A local anesthetic, tetracaine, similarly inhibits Ag+ and K+ contractures in frog skeletal muscle.

“…The local anesthetic also blocked the action potential, with little effect on the resting membrane potential. Such effects of tetracaine on K + contracture are consistent with the findings reported already (LUTTGAU and OETLIKER, 1968;HELLENBRECHT, 1971;CAPUTO, 1972CAPUTO, , 1976ALMERS and BEST, 1976;CAPUTO and BOLANOS, 1987). On the peak amplitude and the duration of Ag contracture and on the contractile threshold for Ag contracture development, tetracaine showed comparable effects with those on K + contracture ( Figs.…”

Effects of caffeine and isoprenaline on mammalian ventricular muscle

“…In skeletal muscle, low concentrations of caffeine have no effect on the resting membrane potential (Luttgau & Oetliker, 1968) and little effect on the action potential (Taylor, Preiser & Sandow, 1969) and the potentiation of contractile force produced by the drug is attributed to an action on sarcoplasmic calcium stores (Weber & Herz, 1968). In atrial muscle, caffeine changes the shape of the action potential (de Gubareff & Sleator, 1965) but it is not clear that this is the primary cause of the increase in amplitude and duration of the muscle contraction; caffeine may act on sarcoplasmic calcium stores, as well as on the cell membrane in cardiac muscle.…”

“…Caffeine increases the force of contraction of both skeletal muscle (Sandow, 1965;Luttgau & Oetliker, 1968) and cardiac muscle (Rail & West, 1963;de Gubareff & Sleator, 1965;Blinks, Olson, Jewell & Braveny, 1972). In skeletal muscle, low concentrations of caffeine have no effect on the resting membrane potential (Luttgau & Oetliker, 1968) and little effect on the action potential (Taylor, Preiser & Sandow, 1969) and the potentiation of contractile force produced by the drug is attributed to an action on sarcoplasmic calcium stores (Weber & Herz, 1968).…”