Activation and Inhibition of Skeletal RyR Channels by a Part of the Skeletal DHPR II-III Loop: Effects of DHPR Ser687 and FKBP12
| Autor: | Suzy M. Pace, Marco G. Casarotto, Esther M. Gallant, Derek R. Laver, Angela F. Dulhunty, Suzanne M. Curtis |
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| Rok vydání: | 1999 |
| Předmět: |
Thapsigargin
Calcium Channels L-Type Stereochemistry Lipid Bilayers Molecular Sequence Data Biophysics Cesium chemistry.chemical_element Calcium Membrane Potentials Tacrolimus Binding Proteins chemistry.chemical_compound Adenosine Triphosphate medicine Animals Magnesium Amino Acid Sequence Immunophilins Muscle Skeletal Receptor Membrane potential Voltage-dependent calcium channel Ryanodine receptor Endoplasmic reticulum Electric Conductivity Skeletal muscle Ryanodine Receptor Calcium Release Channel musculoskeletal system Peptide Fragments Sarcoplasmic Reticulum medicine.anatomical_structure chemistry Calcium Channels Rabbits Research Article |
| Zdroj: | Biophysical Journal. 77(1):189-203 |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/s0006-3495(99)76881-5 |
| Popis: | Peptides, corresponding to sequences in the N-terminal region of the skeletal muscle dihydropyridine receptor (DHPR) II-III loop, have been tested on sarcoplasmic reticulum (SR) Ca2+ release and ryanodine receptor (RyR) activity. The peptides were: A1, Thr671-Leu690; A2, Thr671-Leu690 with Ser687 Ala substitution; NB, Gly689-Lys708 and A1S, scrambled A1 sequence. The relative rates of peptide-induced Ca2+ release from normal (FKBP12+) SR were A2 > A1 > A1S > NB. Removal of FKBP12 reduced the rate of A1-induced Ca2+ release by approximately 30%. A1 and A2 (but not NB or A1S), in the cytoplasmic (cis) solution, either activated or inhibited single FKBP12+ RyRs. Maximum activation was seen at -40 mV, with 10 microM A1 or 50 nM A2. The greatest A1-induced increase in mean current (sixfold) was seen with 100 nM cis Ca2+. Inhibition by A1 was greatest at +40 mV (or when permeant ions flowed from cytoplasm to SR lumen) with 100 microM cis Ca2+, where channel activity was almost fully inhibited. A1 did not activate FKBP12-stripped RyRs, although peptide-induced inhibition remained. The results show that peptide A activation of RyRs does not require DHPR Ser687, but required FKBP12 binding to RyRs. Peptide A must interact with different sites to activate or inhibit RyRs, because current direction-, voltage-, cis [Ca2+]-, and FKBP12-dependence of activation and inhibition differ. |
| Databáze: | OpenAIRE |
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