TY - JOUR
T1 - Epileptiform activity induced by pharmacologic reduction of M-current in the developing hippocampus in vitro
AU - Peña, Fernando
AU - Alavez-Pérez, Noé
PY - 2006/1
Y1 - 2006/1
N2 - Purpose: Benign familial neonatal convulsions (BFNCs), an inheritable epilepsy that occurs in neonates but not in adults, is caused by hypofunctional mutations in genes codifying for the M-type K+ current. In an attempt to develop an in vitro model of this disease, we tested whether blocking M-current with linopirdine induces epileptiform activity in brain slices from animals of different ages. Methods: Horizontal hippocampus-entorhinal cortex slices were obtained from neonatal (1-2 weeks after birth) and adult (8-9 weeks after birth) rats. Extracellular field recordings of the CA1 region were performed. After recording control conditions, linopirdine was added to the bath, and field activity was recorded continuously for 3 h. 4-Aminopyridine, a drug commonly used to induce epileptiform activity in vitro, was used as a control for our experimental conditions. Results: Bath perfusion of linopirdine induced epileptiform activity only in slices from neonatal rats. Epileptiform activity consisted of interictal-like and ictal-like activity. In slices from adult rats, linopirdine induced erratic interictal-like activity. In contrast, 4-aminopyridine was able to induce epileptiform activity in slices from both neonatal and adult rats. Conclusions: We demonstrated that blockade of M-current in vitro produces epileptiform activity with a developmental pattern similar to that observed in BNFCs. This could be an in vitro model that can be used to study the cellular mechanisms of epileptogenesis and the developmental features of BFNCs, as well as to develop some therapeutic strategies.
AB - Purpose: Benign familial neonatal convulsions (BFNCs), an inheritable epilepsy that occurs in neonates but not in adults, is caused by hypofunctional mutations in genes codifying for the M-type K+ current. In an attempt to develop an in vitro model of this disease, we tested whether blocking M-current with linopirdine induces epileptiform activity in brain slices from animals of different ages. Methods: Horizontal hippocampus-entorhinal cortex slices were obtained from neonatal (1-2 weeks after birth) and adult (8-9 weeks after birth) rats. Extracellular field recordings of the CA1 region were performed. After recording control conditions, linopirdine was added to the bath, and field activity was recorded continuously for 3 h. 4-Aminopyridine, a drug commonly used to induce epileptiform activity in vitro, was used as a control for our experimental conditions. Results: Bath perfusion of linopirdine induced epileptiform activity only in slices from neonatal rats. Epileptiform activity consisted of interictal-like and ictal-like activity. In slices from adult rats, linopirdine induced erratic interictal-like activity. In contrast, 4-aminopyridine was able to induce epileptiform activity in slices from both neonatal and adult rats. Conclusions: We demonstrated that blockade of M-current in vitro produces epileptiform activity with a developmental pattern similar to that observed in BNFCs. This could be an in vitro model that can be used to study the cellular mechanisms of epileptogenesis and the developmental features of BFNCs, as well as to develop some therapeutic strategies.
KW - Epileptiform activity
KW - Linopirdine
KW - M-current
KW - Neonatal convulsions
UR - http://www.scopus.com/inward/record.url?scp=33645020074&partnerID=8YFLogxK
U2 - 10.1111/j.1528-1167.2006.00369.x
DO - 10.1111/j.1528-1167.2006.00369.x
M3 - Artículo
C2 - 16417531
AN - SCOPUS:33645020074
SN - 0013-9580
VL - 47
SP - 47
EP - 54
JO - Epilepsia
JF - Epilepsia
IS - 1
ER -