• Patchliner

    兼顾科研与工业的全自动膜片钳系统
  • Patchliner

    自主生产与质量控制的耗材
  • Patchliner

    拥有超过10年实验设计与支持的经验
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    拥有所有手动膜片钳的特征与优点

2016 - The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts

icon pl  Patchliner publication in Epilepsia (2016)

Authors: 
Petty S.J., Milligan C.J., Todaro M., Richards K.L., Kularathna P.K., Pagel C.N., French C.R., Hill-Yardin E.L., O'Brien T.J., Wark J.D., Mackie E.J., Petrou S.

Journal: 
Epilepsia (2016) 57(9):1398-1405


Abstract: 

Objective:
Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage-gated sodium (NaV) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.

Methods:
Immunocytochemistry was performed on primary calvarial osteoblasts extracted from neonatal C57BL/6J mice and additional RNA sequencing (RNASeq) was included to confirm expression of NaV. Whole-cell patch-clamp recordings were made to identify the native currents expressed and to assess the actions of carbamazepine (50 μm) or phenytoin (50 μm).

Results:
NaV expression was demonstrated with immunocytochemistry, RNA sequencing, and functionally, with demonstration of robust tetrodotoxin-sensitive and voltage-activated inward currents. Application of carbamazepine or phenytoin resulted in significant inhibition of current amplitude for carbamazepine (31.6 ± 5.9%, n = 9; p < 0.001), and for phenytoin (35.5 ± 6.9%, n = 7; p < 0.001).

Significance:
Mouse osteoblasts express NaV, and native NaV currents are blocked by carbamazepine and phenytoin, supporting our hypothesis that AEDs can directly influence osteoblast function and potentially affect bone strength.


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