Up-regulation of L-type high voltage-gated calcium channel subunits by sustained exposure to 1,4- and 1,5-benzodiazepines in cerebrocortical neurons.
J Neurochem
; 103(6): 2518-28, 2007 Dec.
Article
en En
| MEDLINE
| ID: mdl-17949410
ABSTRACT
The aim of this study is to examine how sustained exposure to two 1,4-benzodiazepines (BZDs) with different action period, diazepam and brotizolam, and a 1,5-BZD, clobazam, affects L-type high voltage-gated calcium channel (HVCC) functions and its mechanisms using primary cultures of mouse cerebral cortical neurons. The sustained exposure to these three BZDs increased [(45)Ca2+] influx, which was due to the enhanced [(45)Ca2+] entry through L-type HVCCs but not through of Cav2.1 and Cav2.2. Increase in [(3)H]diltiazem binding after the exposure to these three BZDs was due to the increase in the binding sites of [(3)H]diltiazem. Western blot analysis showed increase of Cav1.2 and Cav1.3 in association with the increased expression of alpha2/delta1 subunit. Similar changes in [(3)H]diltiazem binding and L-type HVCC subunit expression were found in the cerebral cortex from mouse with BZD physical dependence. These results indicate that BZDs examined here have the potential to increase L-type HVCC functions mediated via the enhanced expression of not only Cav1.2 and Cav1.3 but also alpha2/delta1 subunit after their sustained exposure, which may participate in the development of physical dependence by these BZDs.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzodiazepinas
/
Canales de Calcio
/
Corteza Cerebral
/
Canales de Calcio Tipo L
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Japón