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Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse
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| Zeitschriftentitel: | Journal of Cell Science |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Journal of Cell Science, 2019 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
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| Schlagwörter: |
| author_facet |
Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. |
|---|---|
| author |
Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. |
| spellingShingle |
Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. Journal of Cell Science Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse Cell Biology |
| author_sort |
salvage, samantha c. |
| spelling |
Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. 1477-9137 0021-9533 The Company of Biologists Cell Biology http://dx.doi.org/10.1242/jcs.229039 <jats:p>Mutations in the cardiac ryanodine receptor calcium release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF). The RyR2-P2328S mutation produces catecholaminergic polymorphic ventricular tachycardia (CPVT) and AF in hearts from RyR2P2328S/P2328S (RyR2S/S) mice. We have now examined P2328S RyR2 channels from RyR2S/S hearts. The activity of wild type (WT) and P2328S RyR2 channels was similar at a cytoplasmic [Ca2+] of 1 mM, but P2328S RyR2 was significantly more active than WT at a cytoplasmic [Ca2+] of 1 µM. This was associated with a &gt;10-fold shift in the AC50 for Ca2+-activation from ∼3.5 µM Ca2+ in WT RyR2 to ∼320 nM in P2328S channels and an unexpected &gt;1000-fold shift in the IC50 for inactivation from ∼50 mM in WT channels to ≤7 µM in P2328S channels, into systolic [Ca2+] levels. Unexpectedly, the shift in Ca2+-activation was not associated with changes in subconductance activity, S2806 or S2814 phosphorylation, or FKBP12 bound to the channels. The changes in channel activity with the P2328S mutation correlate with altered Ca2+ homeostasis in myocytes from RyR2S/S mice and the CPVT and AF phenotypes.</jats:p> Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse Journal of Cell Science |
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| title |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_unstemmed |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_full |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_fullStr |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_full_unstemmed |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_short |
Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_sort |
ion channel gating in cardiac ryanodine receptors from the arrhythmic ryr2-p2328s mouse |
| topic |
Cell Biology |
| url |
http://dx.doi.org/10.1242/jcs.229039 |
| publishDate |
2019 |
| physical |
|
| description |
<jats:p>Mutations in the cardiac ryanodine receptor calcium release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF). The RyR2-P2328S mutation produces catecholaminergic polymorphic ventricular tachycardia (CPVT) and AF in hearts from RyR2P2328S/P2328S (RyR2S/S) mice. We have now examined P2328S RyR2 channels from RyR2S/S hearts. The activity of wild type (WT) and P2328S RyR2 channels was similar at a cytoplasmic [Ca2+] of 1 mM, but P2328S RyR2 was significantly more active than WT at a cytoplasmic [Ca2+] of 1 µM. This was associated with a &gt;10-fold shift in the AC50 for Ca2+-activation from ∼3.5 µM Ca2+ in WT RyR2 to ∼320 nM in P2328S channels and an unexpected &gt;1000-fold shift in the IC50 for inactivation from ∼50 mM in WT channels to ≤7 µM in P2328S channels, into systolic [Ca2+] levels. Unexpectedly, the shift in Ca2+-activation was not associated with changes in subconductance activity, S2806 or S2814 phosphorylation, or FKBP12 bound to the channels. The changes in channel activity with the P2328S mutation correlate with altered Ca2+ homeostasis in myocytes from RyR2S/S mice and the CPVT and AF phenotypes.</jats:p> |
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| author | Salvage, Samantha C., Gallant, Esther M., Beard, Nicole A., Ahmad, Shiraz, Valli, Haseeb, Fraser, James A., Huang, Christopher L.-H, Dulhunty, Angela F. |
| author_facet | Salvage, Samantha C., Gallant, Esther M., Beard, Nicole A., Ahmad, Shiraz, Valli, Haseeb, Fraser, James A., Huang, Christopher L.-H, Dulhunty, Angela F., Salvage, Samantha C., Gallant, Esther M., Beard, Nicole A., Ahmad, Shiraz, Valli, Haseeb, Fraser, James A., Huang, Christopher L.-H, Dulhunty, Angela F. |
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| description | <jats:p>Mutations in the cardiac ryanodine receptor calcium release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF). The RyR2-P2328S mutation produces catecholaminergic polymorphic ventricular tachycardia (CPVT) and AF in hearts from RyR2P2328S/P2328S (RyR2S/S) mice. We have now examined P2328S RyR2 channels from RyR2S/S hearts. The activity of wild type (WT) and P2328S RyR2 channels was similar at a cytoplasmic [Ca2+] of 1 mM, but P2328S RyR2 was significantly more active than WT at a cytoplasmic [Ca2+] of 1 µM. This was associated with a &gt;10-fold shift in the AC50 for Ca2+-activation from ∼3.5 µM Ca2+ in WT RyR2 to ∼320 nM in P2328S channels and an unexpected &gt;1000-fold shift in the IC50 for inactivation from ∼50 mM in WT channels to ≤7 µM in P2328S channels, into systolic [Ca2+] levels. Unexpectedly, the shift in Ca2+-activation was not associated with changes in subconductance activity, S2806 or S2814 phosphorylation, or FKBP12 bound to the channels. The changes in channel activity with the P2328S mutation correlate with altered Ca2+ homeostasis in myocytes from RyR2S/S mice and the CPVT and AF phenotypes.</jats:p> |
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| spelling | Salvage, Samantha C. Gallant, Esther M. Beard, Nicole A. Ahmad, Shiraz Valli, Haseeb Fraser, James A. Huang, Christopher L.-H Dulhunty, Angela F. 1477-9137 0021-9533 The Company of Biologists Cell Biology http://dx.doi.org/10.1242/jcs.229039 <jats:p>Mutations in the cardiac ryanodine receptor calcium release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF). The RyR2-P2328S mutation produces catecholaminergic polymorphic ventricular tachycardia (CPVT) and AF in hearts from RyR2P2328S/P2328S (RyR2S/S) mice. We have now examined P2328S RyR2 channels from RyR2S/S hearts. The activity of wild type (WT) and P2328S RyR2 channels was similar at a cytoplasmic [Ca2+] of 1 mM, but P2328S RyR2 was significantly more active than WT at a cytoplasmic [Ca2+] of 1 µM. This was associated with a &gt;10-fold shift in the AC50 for Ca2+-activation from ∼3.5 µM Ca2+ in WT RyR2 to ∼320 nM in P2328S channels and an unexpected &gt;1000-fold shift in the IC50 for inactivation from ∼50 mM in WT channels to ≤7 µM in P2328S channels, into systolic [Ca2+] levels. Unexpectedly, the shift in Ca2+-activation was not associated with changes in subconductance activity, S2806 or S2814 phosphorylation, or FKBP12 bound to the channels. The changes in channel activity with the P2328S mutation correlate with altered Ca2+ homeostasis in myocytes from RyR2S/S mice and the CPVT and AF phenotypes.</jats:p> Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse Journal of Cell Science |
| spellingShingle | Salvage, Samantha C., Gallant, Esther M., Beard, Nicole A., Ahmad, Shiraz, Valli, Haseeb, Fraser, James A., Huang, Christopher L.-H, Dulhunty, Angela F., Journal of Cell Science, Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse, Cell Biology |
| title | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_full | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_fullStr | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_full_unstemmed | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_short | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| title_sort | ion channel gating in cardiac ryanodine receptors from the arrhythmic ryr2-p2328s mouse |
| title_unstemmed | Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse |
| topic | Cell Biology |
| url | http://dx.doi.org/10.1242/jcs.229039 |