Table 1.
| Protein | Ion Permeability | Features | Inhibitors | Disease Linkage | References | |
|---|---|---|---|---|---|---|
| Cation chloride cotransporters | ||||||
| Potassium Chloride Cotransporters (KCCs) | [57, 77, 86, 134, 259] | |||||
| KCC1 (SLC12A4) | Efflux of K+, Cl- | Ubiquitous | Inhibited by: Furosemide > bumetanide, DIOA, ATP, Hypertonic media, Disulfonic acid stilbene High extracellular K+, WNK, SPAK Activated by: Hypotonic media;N-ethylmaleimide;PDGF (KCC2);PKA (KCC2) |
N/A | [86, 88, 119, 134, 227, 242, 299, 347, 350] | |
| KCC2 (SLC12A5) | Neuronal specific | N/A | [77, 86, 134, 234, 239, 263, 290, 346] | |||
| KCC3 (SLC12A6) | Widespread expression: heart, kidney, neurons, epithelia, red blood cells, muscle, placenta | ACCPN ; variants with bipolar disease | [86, 115, 121, 200, 201, 213, 252] | |||
| KCC4 (SLC12A7) | Widespread expression; weak in brain | N/A | [86, 169, 213, 312] | |||
| Sodium potassium chloride cotransporters (NKCCs) | ||||||
| NKCC1 (SLC12A2; BSC2) | Influx of Na+, K+, 2Cl- | Ubiquitous | Inhibited by: Bumetanide > Furosemide PP-1 Activated by: ATP, Hypertonic media, Calyculin A, Low Cl WNK, SPAK (NKCC1) |
N/A | [49, 59, 77, 134, 210, 240, 246, 247] | |
| NKCC2 (SLC12A1; BSC1) | Kidney | Bartter’s syndrome type I | [76, 126, 188, 259, 284] | |||
| Sodium chloride cotransporters (NCCs) | ||||||
| Sodium chloride co-transporter (SLC12A3; NCC) | Influx of Na+, Cl- | Kidney | Inhibited by: Thiazides Activated by: WNK |
Gitelman’s syndrome | [259] | |
| Chloride channels | ||||||
| Cl- channel 2 (Clcn2 or Clc2) | Efflux of Cl- | Brain (neurons), heart, pancreas, lung, liver, fibroblasts, epithelial | Inhibited by: PP-1 Activated by: Hyperpolarization, cell swelling, acidic pH, hypo-osmotic shock, arachidonic acid, omeprazole, p34(cdc2)/cyclin B; PKA |
Idiopathic generalized epilepsy | [25, 47, 52, 72, 75, 102, 222, 286, 306] | |
| Selected HCO3- transporters | ||||||
| Na+-dependent anion exchanger NDAE (SLC4A8; NDCBE) | Influx Na+, HCO3-; Efflux H+, Cl- |
Brain, testis, kidney, ovary | Inhibited by: DIDS Activated by: ATP requirement (squid) |
N/A | [92, 267,] | |
| Na+-independent anion exchanger AE3 (SLC4A3) | Influx Cl-; Efflux HCO3- | Brain, retina, heart, smooth muscle, epithelia | Activated by: Increased intracellular pH |
Idiopathic generalized epilepsy | [267, 273] | |
Abbreviations: ACCPN: Agenesis of Corpus Callosum with Peripheral Neuropathy; DIDS: 4,4’-diisothiocyano-2,2’-stilbene disulphonic acid; PP-1: protein phosphatase 1; PKA: protein kinase A; PDGF: platelet derived growth factor; WNK: With No lysine (K); SPAK: Serine Proline Alanine lysine (K) rich; OSR: oxidative stress responsive kinase; DIOA: dihydronindenyloxy alkanoic acid.