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1 Neuromuscular Research Laboratory, Maimonides Medical Center, Brooklyn, New York 11219-2999; and 2 Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905-0001
Fast-twitch and slow-twitch rat skeletal muscles produce dissimilar contractures with caffeine. We used digital imaging microscopy to monitor Ca2+ (with fluo 3-acetoxymethyl ester) and sarcomere motion in intact, unrestrained rat muscle fibers to study this difference. Changes in Ca2+ in individual fibers were markedly different from average responses of a population. All fibers showed discrete, nonpropagated, local Ca2+ transients occurring randomly in spots about one sarcomere apart. Caffeine increased local Ca2+ transients and sarcomere motion initially at 4 mM in soleus and 8 mM in extensor digitorum longus (EDL; ~23°C). Ca2+ release subsequently adapted or inactivated; this was surmounted by higher doses. Motion also adapted but was not surmounted. Prolonged exposure to caffeine evidently suppressed myofilament interaction in both types of fiber. In EDL fibers, 16 mM caffeine moderately increased local Ca2+ transients. In soleus fibers, 16 mM caffeine greatly increased Ca2+ release and produced propagated waves of Ca2+ (~1.5-2.5 µm/s). Ca2+ waves in slow-twitch fibers reflect the caffeine-sensitive mechanism of Ca2+-induced Ca2+ release. Fast-twitch fibers possibly lack this mechanism, which could account for their lower sensitivity to caffeine.
dissimilar caffeine sensitivity; calcium release from sarcoplasmic reticulum; parvalbumin
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