Research articleRegulation of the cell surface expression of chloride transporters during epileptogenesis

- Differential alterations in the plasma membrane expression of cation-chloride transporters were observed during epileptogenesis.
- A shift in the cell surface expression of KCC2 and NKCC1 was detected during the early phase of epileptogenesis.
- No change in the cell surface expression of KCC2 or NKCC1 was detected at the chronic stage.
- Hyperexcitability during epileptogenesis may be a cumulative effect of multiple deficits impacting different aspects of GABAergic neurotransmission.

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.