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The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts
Author(s) -
Petty Sandra J.,
Milligan Carol J.,
Todaro Marian,
Richards Kay L.,
Kularathna Pamuditha K.,
Pagel Charles N.,
French Chris R.,
HillYardin Elisa L.,
O'Brien Terence J.,
Wark John D.,
Mackie Eleanor J.,
Petrou Steven
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13474
Subject(s) - carbamazepine , phenytoin , sodium channel , immunocytochemistry , pharmacology , epilepsy , osteoblast , anticonvulsant , tetrodotoxin , medicine , chemistry , neuroscience , biology , biochemistry , sodium , in vitro , organic chemistry
Summary 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 (Na V ) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on Na V channels. Methods Immunocytochemistry was performed on primary calvarial osteoblasts extracted from neonatal C57BL/6J mice and additional RNA sequencing ( RNAS eq) was included to confirm expression of Na V . Whole‐cell patch‐clamp recordings were made to identify the native currents expressed and to assess the actions of carbamazepine (50 μ m ) or phenytoin (50 μ m ). Results Na V 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 Na V , and native Na V currents are blocked by carbamazepine and phenytoin, supporting our hypothesis that AED s can directly influence osteoblast function and potentially affect bone strength.