title: Regulation of the cell surface expression of chloride transporters during epileptogenesis.
abstract: The process is commonly known as epileptogenesis refers to the cascade of molecular and cellular changes that transform the brain to make it hyperexcitable and capable of generate recurrent spontaneous seizures. Unfortunately, our understanding of the molecular changes that affect the brain during epileptogenesis remains incomplete. Recent evidence suggests that dysfunction of cation-chloride transporters (CCCs) might be one of the factors that contribute to the deficits in inhibitory neurotransmission observed during epileptogenesis. This study analyzed the cell surface expression of CCCs during epileptogenesis and during chronic epilepsy to evaluate if a loss of CCCs from the plasma membrane might contribute to hyperexcitability. Alterations in the plasma membrane expression of CCCs were mostly detected during the early phase of the epileptogenic period, suggesting that dysfunction of CCCs might contribute to the alterations in the chloride gradient previously detected. Together, the findings presented here suggest that aberrant regulation of the plasma membrane levels of CCCs might contribute to the impartment of GABAergic neurotransmission and that CCCs dysfunction might be relevant for the initial appearance of spontaneous seizures.
authors.affiliation: Department of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, 80045 USA. Electronic address: marco.gonzalez@ucdenver.edu.
authors.forename: Marco I
authors.initials: MI
authors.lastname: González
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism* / Q000503:physiopathology; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C578879:Slc12a2 protein, rat
keywords: Epileptogenesis; KCC2; NKCC1; Transporter trafficking