Actions of caffeine on fast‐ and slow‐twitch muscles of the rat.

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Abstract
1. The effects of caffeine (0.2‐20 mmol l‐1) have been examined on calcium transients (measured with aequorin) and isometric force in intact bundles of fibres from soleus (slow‐twitch) and extensor digitorum longus (EDL; fast‐twitch) muscles of the rat. 2. At 25 degrees C, threshold caffeine concentration for an observable increase in resting [Ca2+]i was 0.2 and 1.0 mmol l‐1 for soleus and EDL muscles respectively. Increases in resting force were first detectable at about 0.5 mmol l‐1 caffeine for soleus muscles and 5.0 mmol l‐1 caffeine for EDL muscles and occurred in the range 0.2‐0.4 mumol l‐1 [Ca2+]i for soleus and 0.7‐0.9 mumol l‐1 for EDL. 3. Caffeine potentiated the twitch responses of soleus and EDL in a dose‐related manner. The soleus was more sensitive in this respect, with 50% potentiation occurring at 1 mmol l‐1 caffeine compared with 3.5 mmol l‐1 for the EDL. Concentrations of caffeine below 2 mmol l‐1 potentiated Ca2+ transients associated with twitches in both soleus and EDL muscles with no apparent change in the decay rate constant. 4. High concentrations of caffeine (greater than 2 mmol l‐1) further potentiated peak Ca2+ in the EDL but depressed it in the soleus. The rate of decay of the Ca2+ transient in high caffeine was significantly prolonged in the soleus but remained unaffected in the EDL. 5. The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine (IBMX) had little effect on force or [Ca2+]i at concentrations known to significantly increase intracellular cyclic AMP levels. 6. The Ca2+ transient during fused tetani was characterized by an initial peak, a decline to a plateau level and sometimes a gradual rise towards the end of the stimulus train. Peak [Ca2+]i during normal tetani ranged between 1.1 and 2.4 mumol l‐1 in the soleus and 1.9 and 4.0 mumol l‐1 in the EDL. 7. Caffeine potentiated both force and [Ca2+]i during tetanus. Since the increase of the Ca2+ transient was significantly greater than potentiation of force, it is likely that saturation of myofilaments occurs. The primary effect of caffeine on the Ca2+ transient was an elevation of the plateau phase. 8. Caffeine concentrations below 5 mmol l‐1 potentiate twitch and tetanic force in both fast‐ and slow‐twitch mammalian skeletal muscles primarily by increasing both the basal and stimulus‐evoked release of Ca2+ from the sarcoplasmic reticulum.