التفاصيل البيبلوغرافية
| العنوان: |
Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent kinase inhibitor roscovitine |
| المؤلفون: |
Buraei, Z., Anghelescu, Mircea, Elmslie, K. S. |
| المصدر: |
PCOM Scholarly Papers |
| سنة النشر: |
2005 |
| المجموعة: |
Philadelphia College of Osteopathic Medicine: DigitalCommons@PCOM |
| مصطلحات موضوعية: |
4 dihydro 2, 6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, calcium channel N type, cyclin dependent kinase 1, cyclin dependent kinase 2, cyclin dependent kinase 3, cyclin dependent kinase inhibitor, roscovitine, voltage gated calcium channel, animal cell, article, binding site, calcium current, channel gating, controlled study, enzyme inhibition, extracellular space, model, nonhuman, Action Potentials, Animals, Calcium, Calcium Channels, N-Type, P-Type, Q-Type, Computer Simulation, Cyclin-Dependent Kinases, Dose-Response Relationship |
| الوقت: |
1 |
| الوصف: |
The lack of a calcium channel agonist (e.g., BayK8644) for CaV2 channels has impeded their investigation. Roscovitine, a potent inhibitor of cyclin-dependent kinases 1, 2, and 5, has recently been reported to slow the deactivation of P/Q-type calcium channels (CaV2.1). We show that roscovitine also slows deactivation (EC50 ~53 µM) of N-type calcium channels (CaV2.2) and investigate gating alterations induced by roscovitine. The onset of slowed deactivation was rapid (~2 s), which contrasts with a slower effect of roscovitine to inhibit N-current (EC50 ~300 µM). Slow deactivation was specific to roscovitine, since it could not be induced by a closely related cyclin-dependent kinase inhibitor, olomoucine (300 µM). Intracellularly applied roscovitine failed to slow deactivation, which implies an extracellular binding site. The roscovitine-induced slow deactivation was accompanied by a slight left shift in the activation-voltage relationship, slower activation at negative potentials, and increased inactivation. Additional data showed that roscovitine preferentially binds to the open channel to slow deactivation. A model where roscovitine reduced a backward rate constant between two open states was able to reproduce the effect of roscovitine on both activation and deactivation. © 2005 by the Biophysical Society. |
| نوع الوثيقة: |
text |
| اللغة: |
unknown |
| العلاقة: |
https://digitalcommons.pcom.edu/scholarly_papers/1522Test |
| الإتاحة: |
https://digitalcommons.pcom.edu/scholarly_papers/1522Test |
| رقم الانضمام: |
edsbas.8DA2BD9D |
| قاعدة البيانات: |
BASE |
