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| The EMBO Journal
(1997) 16, 6956–6963, doi:10.1093/emboj/16.23.6956 |
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| Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles |
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| Federica Bertocchini1, Catherine E. Ovitt2, Antonio Conti1, Virginia Barone1, Hans R. Schöler2, Roberto Bottinelli3, Carlo Reggiani3 and Vincenzo Sorrentino1, 4 |
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1 DIBIT, San Raffaele Scientific Institute, Milano, Germany 2 European Molecular Biology Laboratory, Heidelberg, Germany 3 Institute of Human Physiology, University of Pavia, Pavia, Italy 4 Institute of Histology, University of Siena, Siena, Italy To whom correspondence should be addressed Vincenzo Sorrentino, sorrenv@dibit.hsr.it Received 20 June 1997; Revised 10 September 1997. |
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| Abstract |
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| The skeletal isoform of Ca2+ release channel, RyR1, plays a central role in activation of skeletal muscle contraction. Another isoform, RyR3, has been observed recently in some mammalian skeletal muscles, but whether it participates in regulating skeletal muscle contraction is not known. The expression of RyR3 in skeletal muscles was studied in mice from late fetal stages to adult life. RyR3 was found to be expressed widely in murine skeletal muscles during the post-natal phase of muscle development, but was not detectable in muscles of adult mice, with the exception of the diaphragm and soleus muscles. RyR3 knockout mice were generated, and it was shown that skeletal muscle contraction in these mice was impaired during the first weeks after birth. In skeletal muscles isolated from newborn RyR3-/- mice, but not in those from adult mice, the twitch elicited by electrical stimulation and the contracture induced by caffeine were strongly depressed. These results provide the first evidence that RyR3 has a physiological role in excitation–contraction coupling of neonatal skeletal muscles. The disproportion between the low amount of RyR3 and the large impact of the RyR3 knockout suggests that this isoform contributes to the amplification of Ca2+ released by the existing population of ryanodine receptors (RyR1). |
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| Keywords: Ca2+ release channels, muscle contraction, muscle development, ryanodine receptors |
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