Table I.

Selected proteins involved in Cl- homeostasis with known effects on GABA_A signaling.

Protein	Function	Disease linkage	References
Favoring hyperpolarizing GABA_A responses

Potassium Chloride co-transporters (KCCs)	Efflux of K⁺ and Cl⁻	Humans: Agenesis of corpus callosum with peripheral neuropathy and variants with bipolar disease	(Payne et al. 1996; Delpire and Mount 2002; Howard et al. 2002; Meyer et al. 2005; Salin-Cantegrel et al. 2007)
		Knockout mice epilepsy

Chloride channel 2	Efflux of Cl⁻	Humans: Idiopathic generalized epilepsy; Lesion-related epilepsy.	(Haug et al. 2003; D'Agostino et al. 2004; Niemeyer et al. 2004; Bertelli et al. 2007; Blanz et al. 2007; Everett et al. 2007)
		Knockout mice: Vacuolar leukoencephalopathy, bindness, decreased conduction velocity in central auditory paths, normal neuronal morphology.

Na⁺ dependent anion exchanger	Influx of Na⁺ , HCO3⁻ ; Efflux of H⁺ , Cl⁻.	N/A	(Kintner et al. 2007)

Favoring depolarizing GABA_A responses

Sodium potassium chloride cotransporters (NKCCs)	Influx of Na⁺, K⁺and 2Cl⁻	Humans: Bartter’s syndrome type 1	(Delpire and Mount 2002)

Sodium chloride cotransporters (NCCs)	Influx of Na⁺, and Cl⁻	Humans: Gitelman’s syndrome	(Nicolet-Barousse et al. 2005)

Na⁺ independent anion exchanger	Influx of Cl⁻ ; Efflux of HCO3⁻.	Humans: small susceptibility to Idiopathic generalized epilepsy (AE3).	(Sander et al. 2002; Hentschke et al. 2006)
		Knockout mice: Reduced seizure threshold	(Sander et al. 2002; Hentschke et al. 2006)