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1 Institute of Human Physiology, University of Pavia, I-27100 Pavia; 2 Dipartimento Ricerca Biologica e Tecnologica, Istituto Scientifico San Raffaele, I-20100 Milan; 3 Molecular Medicine Section, Department of Neuroscience, University of Siena, I-53100 Siena; and 4 Department of Anatomy and Physiology, University of Padua, I-35131 Padua, Italy
The response to caffeine was studied in mouse muscles
[diaphragm, soleus, and extensor digitorum longus (EDL)] with
different ryanodine receptor isoform (RyR1, RyR3) composition and in
single permeabilized muscle fibers dissected from diaphragm of
wild-type (WT) and RyR3-deficient (RyR3
/) mice at 1, 15, 30, and 60 postnatal days (PND). The caffeine response decreased during
development, and, in adult mice, was greater in diaphragm, lower in
EDL, and intermediate in soleus. This suggests a direct relation
between response to caffeine and RyR3 expression. The lack of RyR3
reduced caffeine response in young, but not in adult mice, and did not abolish the age-dependent variation and the intermuscle differences. In
diaphragm single fibers, the response to caffeine increased during
development and was reduced in fibers lacking RyR3 both at 15 and 60 PND. A population of fibers highly responsive to caffeine was present
in adult WT and disappeared in RyR3/. The results confirm the
contribution of RyR3 to calcium release for contractile response and
clarify the contribution of RyR3 to developmental changes and
intermuscle differences.
calcium release; contractile response; developmental changes; intermuscle differences; caffeine
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