The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts
AuthorPetty, SJ; Milligan, CJ; Todaro, M; Richards, KL; Kularathna, PK; Pagel, CN; French, CR; Hill-Yardin, EL; O'Brien, TJ; Wark, JD; ...
University of Melbourne Author/sO'Brien, Terence; Pagel, Charles; Todaro, Marian; Hill, Elisa; French, Christopher; Petrou, Steven; Wark, John; Mackie, Eleanor; Petty, Sandra
AffiliationFlorey Department of Neuroscience and Mental Health
Anatomy and Neuroscience
Document TypeJournal Article
CitationsPetty, 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. (2016). The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts. EPILEPSIA, 57 (9), pp.1398-1405. https://doi.org/10.1111/epi.13474.
Access StatusOpen Access
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.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References
- Florey Department of Neuroscience and Mental Health - Research Publications 
- Medical Education - Research Publications 
- Medicine (RMH) - Research Publications 
- Anatomy and Neuroscience - Research Publications 
- Veterinary Biosciences - Research Publications 
- Minerva Elements Records