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| The EMBO Journal
(1998) 17, 2790–2798, doi:10.1093/emboj/17.10.2790 |
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| Functional properties of the ryanodine receptor type 3 (RyR3) Ca2+ release channel |
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| Alois Sonnleitner1, Antonio Conti2, Federica Bertocchini2, Hansgeorg Schindler1 and Vincenzo Sorrentino2, 3 |
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1 Institute for Biophysics, University of Linz, Austria 2 DIBIT, San Raffaele Scientific Institute, Milan Italy 3 Department of Biomedical Sciences, School of Medicine, University of Siena, Siena, Italy To whom correspondence should be addressed Vincenzo Sorrentino, sorrenv@dibit.hsr.it Received 13 August 1997; Revised 20 March 1998; Accepted 24 March 1998. |
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| Abstract |
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| Single-channel analysis of sarcoplasmic reticulum vesicles prepared from diaphragm muscle, which contains both RyR1 and RyR3 isoforms, revealed the presence of two functionally distinct ryanodine receptor calcium release channels. In addition to channels with properties typical of RyR1 channels, a second population of ryanodine-sensitive channels with properties distinct from those of RyR1 channels was observed. The novel channels displayed close-to-zero open-probability at nanomolar Ca2+ concentrations in the presence of 1 mM ATP, but were shifted to the open conformation by increasing Ca2+ to micromolar levels and were not inhibited at higher Ca2+ concentrations. These novel channels were sensitive to the stimulatory effects of cyclic adenosine 5'-diphosphoribose (cADPR). Detection of this second population of RyR channels in lipid bilayers was always associated with the presence of the RyR3 isoform in muscle preparations used for single-channel measurements and was abrogated by the knockout of the RyR3 gene in mice. Based on the above, we associated the novel population of channels with the RyR3 isoform of Ca2+ release channels. The functional properties of the RyR3 channels are in agreement with a potential qualitative contribution of this channel to Ca2+ release in skeletal muscle and in other tissues. |
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| Keywords: Ca2+-release channels, Ca2+ signalling, cyclic adenosine 5'-diphosphoribose, ryanodine receptor type 3 |
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