Premium
A negatively charged region of the skeletal muscle ryanodine receptor is involved in Ca 2+ ‐dependent regulation of the Ca 2+ release channel
Author(s) -
Hayek Salim M.,
Zhao Jiying,
Bhat Manjunatha,
Xu Xuehong,
Nagaraj Ramakrishnan,
Pan Zui,
Takeshima Hiroshi,
Ma Jianjie
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01464-7
Subject(s) - ryr1 , ryanodine receptor , ryanodine receptor 2 , chemistry , skeletal muscle , biophysics , calcium , biochemistry , receptor , biology , endocrinology , organic chemistry
The ryanodine receptor/Ca 2+ release channels from skeletal (RyR1) and cardiac (RyR2) muscle cells exhibit different inactivation profiles by cytosolic Ca 2+ . D3 is one of the divergent regions between RyR1 (amino acids (aa) 1872–1923) and RyR2 (aa 1852–1890) and may contain putative binding site(s) for Ca 2+ ‐dependent inactivation of RyR. To test this possibility, we have deleted the D3 region from RyR1 (ΔD3‐RyR1), residues 1038–3355 from RyR2 (Δ(1038–3355)‐RyR2) and inserted the skeletal D3 into Δ(1038–3355)‐RyR2 to generate sD3‐RyR2. The channels formed by ΔD3‐RyR1 and Δ(1038–3355)‐RyR2 are resistant to inactivation by mM [Ca 2+ ], whereas the chimeric sD3‐RyR2 channel exhibits significant inactivation at mM [Ca 2+ ]. The ΔD3‐RyR1 channel retains its sensitivity to activation by caffeine, but is resistant to inactivation by Mg 2+ . The data suggest that the skeletal D3 region is involved in the Ca 2+ ‐dependent regulation of the RyR1 channel.