Characterization of a calcium-regulation domain of the skeletal-muscle ryanodine receptor
| Autor: | Hayek, S M, Zhu, X, Bhat, M B, Zhao, J, Takeshima, H, Valdivia, H H, Ma, J |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Ryanodine
Lipid Bilayers Ryanodine Receptor Calcium Release Channel CHO Cells musculoskeletal system Membrane Potentials Protein Structure Tertiary Caffeine Cricetinae Animals Calcium Magnesium Calcium Channels Muscle Skeletal tissues Ion Channel Gating Research Article Protein Binding Sequence Deletion |
| ISSN: | 1872-1923 |
| Popis: | A negatively charged region of the N-terminal portion of the skeletal ryanodine receptor (RyR), located between residues 1872-1923, is involved in Ca (2+)-dependent regulation of the Ca(2+)-release channel. This region is divergent between the skeletal (RyR1) and cardiac (RyR2) isoforms of the channel, and is known as D3. Ca(2+) exerts important regulatory functions on the RyR, being involved in both activation and inactivation functions of the channel, i.e. the effects occurring at micromolar and millimolar Ca(2+) concentrations respectively. To characterize the role of D3 in the Ca(2+)-dependent regulation of the Ca(2+)-release channel, we studied the functional consequences of deleting the D3 region from RyR1 (DeltaD3-RyR1) using a heterologous expression system, [(3)H]ryanodine binding assays and single-channel recordings in lipid bilayers. Deletion of the D3 region selectively affected Ca(2+)-dependent regulation of RyR1, but did not alter [(3)H]ryanodine binding or the effect of other modulators on the RyR. Compared with full-length RyR1 (wt-RyR1), the Ca(2+)-dependence curve of DeltaD3-RyR1 is broader, reflecting increased sensitivity to Ca(2+) activation and decreased sensitivity to Ca(2+) inactivation. In addition, DeltaD3-RyR1 was more resistant to inhibition by Mg(2+). Comparison of the effect of caffeine on wt-RyR1 and DeltaD3-RyR1 suggested that D3 is an important region of RyR that participates in Ca(2+)-dependent activation and inactivation of the Ca(2+)-release channel. |
| Databáze: | OpenAIRE |
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