Potassium Channel Genes and Ancillary Subunits: Localization, Modulators, and Diseases
| Type | Gene | Nomenclature | Chromosome | Tissue Expression | Modulators | Disorder/Mechanisms | References |
|---|---|---|---|---|---|---|---|
| Voltage-gated K+ channels (Shaker) | KCNA1 | Kv1.1 | 12p13 | Neurons, heart, retina, pancreatic islet | Blocker: α-DTX, HgTX1, MgTX | Episodic ataxia/myokymia syndrome Missense mutations (11 variants) |
Ramashwami et al., 1990
Litt et al., 1994 Browne et al., 1994, 1995 Adelman et al., 1995 Albrecht et al., 1995 Comu et al., 1996 Boland et al., 1999 D'Adamo et al., 1999 |
| KCNA2 | Kv1.2 | 1 | Brain, heart, pancreatic islet | Blocker: CTX, α-DTX, HgTX1, MgTX, NxTX |
Ramashwami et al., 1990
Klocke et al., 1993 | ||
| KCNA3 | Kv1.3 | 1p21-p13.3 | Lymphocyte, brain, lung, thymus, spleen | Blocker: AgTX2, α-DTX, HgTX1, KTX, MgTX, CTX, NxTX, UK78282, WIN 17317-3, correolide |
Grissmer et al., 1990
Attali et al., 1992 Folander et al., 1994 Hanson et al., 1999 | ||
| KCNA4 | Kv1.4 | 11q13.4-q14.1 | Brain, heart, pancreatic islet | Blocker: UK78282 |
Tamkun et al., 1991
Philipson et al., 1993 Hanson et al., 1999 | ||
| KCNA5 | Kv1.5 | 12p13 | Brain, heart, kidney, lung, skeletal muscle | Blocker: 4-AP, clofilium, loratadine, perhexiline |
Curran et al., 1992
Phromchotikul et al., 1993 Albrecht et al., 1995 | ||
| KCNA6 | Kv1.6 | 12p13 | Brain | Blocker: α-DTX |
Grupe et al., 1990
Klocke et al., 1993 Albrecht et al., 1995 | ||
| KCNA7 | Kv1.7 | 19q13.3 | Heart, pancreatic islet, skeletal muscle | Blocker: 4-AP, capsaicin, tedisamil, NxTX, MgTX | Kalman et al., 1998 | ||
| Voltage- and cGMP-gated K+ channel | KCNA10 | Kv1.10 | 1p13.1 | Aorta, brain, kidney | a. Blocker: 4-AP, CTX, ketoconazole, pimozide b. Opener: cGMP |
Yao et al., 1995
Orias et al., 1997a Lang et al., 2000 | |
| β-subunits for Kv channels | KCNAB1 | Kvβ1 | 3q26.1 | Brain (Kvβ1.1) Heart (Kvβ1.2) |
Rettig et al., 1994
England et al., 1995 McCormack et al., 1995 Majumder et al., 1995 Leicher et al., 1996 Schultz et al., 1996 | ||
| KCNAB2 | Kvβ2 | 1p36.3 | Brain, heart |
Scott et al., 1994
McCormack et al., 1995 Morales et al., 1995 Schultz et al., 1996 | |||
| KCNAB3 | Kvβ3 | 17p13.1 | Brain | Leicher et al., 1998 | |||
| Shab | KCNB1 | Kv2.1-Kv2.2 | 20q13.2 | Brain, heart, kidney, skeletal muscle, retina | Blocker: hanatoxin, TEA |
Frech et al., 1989
Hwang et al., 1992 Melis et al., 1995 | |
| Shaw | KCNC1 | Kv3.1 | 11p15 | Brain, muscle, lymphocyte | Blocker: 4-AP |
Yokoyama et al., 1989
Grissmer et al., 1992 | |
| KCNC2 | Kv3.2 | 19q13.3-q13.4 | Brain | Blocker: 4-AP |
Yokoyama et al., 1989
Ito et al., 1992 Haas et al., 1993 | ||
| KCNC3 | Kv3.3 | 19q13.3-q13.4 | Brain, liver | Blocker: 4-AP |
Ghanshani et al., 1992
Ito et al., 1992 Haas et al., 1993 | ||
| KCNC4 | Kv3.4 | 1p21 | Brain, skeletal muscle | Blocker: 4-AP |
Ghanshani et al., 1992
Klocke et al., 1993 | ||
| Shal | KCND1 | Kv4.1 | Xp11.23-p11.3 | Heart, brain, liver, kidney, lung, placenta, pancreas | Blocker: 4-AP |
Serodio et al., 1994
Isbrandt et al., 2000 | |
| KCND2 | Kv4.2 | 7q31-32 | Brain | Blocker: 4-AP, PaTX |
Diochot et al., 1999
Zhu et al., 1999b Postma et al., 2000 | ||
| KCND3 | Kv4.3 | 1p13.2 | Heart, brain | Blocker: 4-AP, PaTX | Kong et al., 1998 | ||
|
Diochot et al., 1999
Postma et al., 2000 | |||||||
| Kv5.1 | Brain | Drewe et al., 1992 | |||||
| Kv6.1 | Brain | Drewe et al., 1992 | |||||
| KCNF2 | Kv6.2 | 18q22-18q23 | Heart | Zhu et al., 1999a | |||
| Kv8.1 | 8q22.3-8q24.1 | Brain | Hugnot et al., 1996 | ||||
| KCNS1 | Kv9.1 | Brain | Salinas et al., 1997 | ||||
| KCNS2 | Kv9.2 | 8q22 | Brain | Salinas et al., 1997 | |||
| KCNS3 | Kv9.3 | 2p24 | Lung, brain, artery | Patel et al., 1997 | |||
| KCNF1 | KH1 | 2p25 | Heart, skeletal muscle | Su et al., 1997 | |||
| KCNG1 | KH2 | 20q13 | Brain, placenta, skeletal muscle | Su et al., 1997 | |||
| Ether-a-go-go | KCNH1 | EAG | 1q32-q41 | Brain |
Warmke and Ganetzky, 1994
Occhiodoro et al., 1998 | ||
| Humanether-a-go-go | KCNH2 | hERG | 7q35-q36 | Brain, heart | Blocker: clofilium, dofetilide, E4031, LY97241, terfenadine, sertindole | LQT2 a. Missense mutations (7 variants) b. Deletion (2 variants) c. Substitution in intron 3 |
Jiang et al., 1994
Warmke and Ganetzky, 1994 Curran et al., 1995 Benson et al., 1996 Satler et al., 1996 Itoh et al., 1998 Lee-Chen et al., 1999 Jongbloed et al., 1999 Larsen et al., 2000 |
| KCNH3 | BEC1 | 12q13 | Brain |
Banfi et al., 1996
Miyake et al., 1999 | |||
| KCNH4 | BEC2 | Brain | Miyake et al., 1999 | ||||
| MinK | KCNE1 | MinK | 21q22.1-q22.2 | Kidney, uterus, heart, cochlea, retina | LQT5 Missense mutations (5 variants) |
Murai et al., 1989
Chevillard et al., 1993 Schulze-Bahr et al., 1997 Splawski et al., 1997b Duggal et al., 1998 Tyson et al., 1997 | |
| KCNE2 | MinK-related peptide I (MiRP1) | 21q22.1 | LQT6 Missense mutations (3 variants) | Abbott et al., 1999 | |||
| KCNE3 | MiRP2 | Small intestine, colon, kidney | Schroeder et al., 2000b | ||||
| KvLQT1 | KCNQ1 | KvLQT1 | 11p15.5 | Heart, cochlea, kidney, lung, placenta, colon | a. Blocker: chromanol-293B b. Opener: L-364,373, stilbenes, fenamates | LQT1; Jervell-Lange Neilsen syndrome a. Missense mutations (17 variants) b. Deletions (6 variants) c. Insertions (2 variants) d. Insertion/deletion (1 variant) e. Splice variant (1) |
Russell et al., 1996
Wang et al., 1996 Donger et al., 1997 Neyroud et al., 1997 Splawski et al., 1997a Yang et al., 1997 Ackerman et al., 1998 Kanters et al., 1998 Li et al., 1998 Neyroud et al., 1998 Priori et al., 1998 Splawski et al., 1998 Ackerman et al., 1999 Chen et al., 1999c Jongbloed et al., 1999 Larsen et al., 1999 Murray et al., 1999 Neyroud et al., 1999 |
| KCNQ2 | KvLQT2 | 20q13.3 | Brain, neuron | a. Blocker: TEA, linopirdine, XE991, L-735,821 b. Opener: retigabine | Benign neonatal epilepsy a. Missense mutation (2 variants) b. Insertion (1 variant) c. Deletion (1 variant) |
Biervert et al., 1998
Singh et al., 1998 Tinel et al., 1998 Yang et al., 1998 Biervert and Steinlein, 1999 Cooper et al., 2000 | |
| KCNQ3 | KvLQT3 | 8q24 | Brain, neuron | a. Blocker: TEA, linopirdine, XE991 b. Opener: retigabine | Benign neonatal epilepsy Missense mutation (2 variants) |
Charlier et al., 1998
Hirose et al., 2000 | |
| KCNQ4 | KvLQT4 | 1p34 | Outer hair cells, inner ear, central auditory pathway | Hearing loss a. Missense mutation (6 variants) b. Deletion (1 variant) |
Coucke et al., 1999
Kubisch et al., 1999 Talebizadeh et al., 1999 Van Hauwe et al., 2000 | ||
| KCNQ5 | KvLQT5 | 6q14 | Brain, skeletal muscle | Blocker: linopirdine |
Lerche et al., 2000
Schroeder et al., 2000a | ||
| Inward rectifier | KCNJ1 | Kir1.1-Kir1.3 | 11q24 | Kidney, pancreatic islets | Blocker: Ba2+ | Bartter's syndrome, type 2; Bartter's syndrome, antenatal onset a. Missense mutation (9 variants) b. Deletion (2 variants) |
Ho et al., 1993
Shuck et al., 1994 Yano et al., 1994 Krishnan et al., 1995 Simon et al., 1996b Feldmann et al., 1998 |
| KCNJ2 | Kir2.1 | Heart, brain, smooth muscle, skeletal muscle, lung, placenta, kidney | Blocker: Ba2+, spermine, spermidine, Mg2+ |
Kubo et al., 1993a
Raab-Graham et al., 1994 | |||
| KCNJ3 | Kir3.1 | 2q24.1 | Heart, cerebellum | Blocker: Ba2+ |
Kubo et al., 1993b
Stoffel et al., 1994 Schoots et al., 1996 Schoots et al., 1997 | ||
| KCNJ4 | Kir2.3 | 22q13.1 | Heart, brain, skeletal muscle | Blocker: Ba2+ |
Makhina et al., 1994
Perier et al., 1994 Budarf et al., 1995 | ||
| KCNJ5 | Kir3.4 | 11q24 | Heart, pancreas | Blocker: Ba2+, Cs+ | Tucker et al., 1995 | ||
| KCNJ6 | Kir3.2 | 21q22.1-q22.2 | Cerebellum, pancreatic islet | Blocker: Ba2+, Cs+ | Mouseweaver
Missense mutation (1 variant) |
Lesage et al., 1994
Sakura et al., 1995 Patil et al., 1995 Tsaur et al., 1995 | |
| KCNJ8 | Kir6.1/uKATP-1 | 12p11.23 | Various | Blocker: Ba2+, Cs+ |
Inagaki et al., 1995b
Inagaki et al., 1995c Erginel-Unaltuna et al., 1998 | ||
| KCNJ9 | Kir3.3 | 1q21-23 | Brain | Blocker: Ba2+, Cs+ |
Lesage et al., 1994
Kobayashi et al., 1995 Vaughn et al., 2000 | ||
| KCNJ10 | Kir4.1 | 1q | Glia | Blocker: Ba2+, Cs+ |
Takumi et al., 1995
Tada et al., 1997 | ||
| KCNJ11 | Kir6.2 (subunit of KATP channel) | 11p15.1 | Various | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) a. Nonsense mutation (1 variant) b. Missense mutation (1 variant) |
Inagaki et al., 1995a
Thomas et al., 1995a Thomas et al., 1996a Nestorowicz et al., 1997 | ||
| KCNJ12 | Kir2.2 | 17p11.2-p11.1 | Atrium, ventricle | Blocker: Ba2+, Cs+ |
Wible et al., 1995
Hugnot et al., 1997 Namba et al., 1997 | ||
| KCNJ13 | Kir7.1 | 2q37 | GI, kidney, cerebellum, hippocampus, thyroid | Blocker: Ba2+, Cs+ |
Derst et al., 1998
Krapivinsky et al., 1998 Partiseti et al., 1998 Nakamura et al., 1999 | ||
| KCNJ14 | Kir2.4 | 19q13 | Brain, retina | Blocker: Ba2+, Cs+ |
Topert et al., 1998
Hughes et al., 2000 Topert et al., 2000 | ||
| KCNJ15 | Kir4.2 | 21q22.2 | Kidney, lung, brain | Gosset et al., 1997 | |||
| Kir5.1 | Brain, periphery |
Bond et al., 1994
Suzuki et al., 1999 | |||||
| Sulfonylurea receptor | SUR1 | Sulfonylurea receptor 1 (subunit of KATP channel) | 11p15.1 | Pancreas, neurons, skeletal muscle | a. Blocker: glyburide, tolbutamide, glipizide, ciclazindol b. Opener: diazoxide | PHHI a. Missense mutations (11 variants) b. Deletion (4 variants) |
Aguilar-Bryan et al., 1995
Thomas et al., 1995b Thomas et al., 1995a Nestorowicz et al., 1996 Thomas et al., 1996b Glaser et al., 1999 Dunne et al., 1997 Verkarre et al., 1998 Otonkoski et al., 1999 Tanizawa et al., 2000 |
| SUR2 | Sulfonylurea receptor 2 (2A, 2B) (subunit of KATP channel) | 12p12.1 | 2A: Heart, skeletal muscle 2B: Brain, liver, skeletal and smooth muscle | a. Blocker: glyburide, ciclazindole b. Opener: P1075, pinacidil, cromakalim |
Chutkow et al., 1996
Inagaki et al., 1996 Isomoto et al., 1996 | ||
| Large conductance Ca2+-activated | KCNMA1 |
Slo
(BKCachannel α-subunit) | 10q23.1 | Brain, smooth muscle, cochlea, pancreatic islets | a. Blocker: IBTX, CTX, TEA b. Opener: NS1619, NS8, BMS-204352, dehydrosoyasaponin I |
Dworetzky et al., 1994
Pallanck and Ganetzky, 1994 Tseng-Crank et al., 1994 McCobb et al., 1995 Ferrer et al., 1996 Vogalis et al., 1996 Bowles et al., 2000 | |
| KCNMB1 | BKCa β1-subunit | 5q34 | Smooth and skeletal muscle |
Knaus et al., 1994
Tseng-Crank et al., 1996 Jiang et al., 1999 | |||
| KCNMB2 | BKCa β2-subunit | Kidney, heart, uterus, small intestine |
Wallner et al., 1999a
Uebele et al., 2000 | ||||
| KCNMB3 | BKCaβ3-subunit | 3q26.3-q27 | Testis |
Riazi et al., 1999
Behrens et al., 2000 Brenner et al., 2000 Uebele et al., 2000 | |||
| KCNMB4 | BKCaβ4-subunit | 12q14.1-q15 | Brain, heart, kidney, lung |
Behrens et al., 2000
Brenner et al., 2000 Meera et al., 2000 Weiger et al., 2000 | |||
| Small conductance Ca2+-activated | KCNN1 | SK1 | 19p13.1 | Brain, heart | a. Blocker: tubocurarine, dequalinium, UCL 1848 |
Kohler et al., 1996
Litt et al., 1999 Shah and Haylett, 2000 | |
| KCNN2 | SK2 | Brain, adrenal gland, Jurkat T cells | a. Blocker: apamin, ScTX, d-tubocurarine, 4-AP b. Opener: chlorzoxazone, zoxazolamine, 1-EBIO |
Kohler et al., 1996
Jager et al., 2000 Syme et al., 2000 | |||
| KCNN3 | SK3 | 1q21.3 | Brain, heart, liver | Blocker: apamin |
Kohler et al., 1996
Chandy et al., 1998 Wittekindt et al., 1998 Antonarakis et al., 1999 Austin et al., 1999 | ||
| Intermediate conductance Ca2+-activated | KCNN4 | IKCa1 | 19q13.2 | T lymphocytes, colon, smooth muscles, prostate, red blood cells, neurons, placenta, thymus | a. Blocker: CTX, clotrimazole, nitrendipine, miconazole, cetiedil, econazole, TRAM-34 b. Opener: 1-EBIO, chlorzoxazone, zoxazolamine |
Ishii et al., 1997
Joiner et al., 1997 Logsdon et al., 1997 Ghanshani et al., 1998 Jensen et al., 1998 Neylon et al., 1999 Wulff et al., 2000 | |
| Two-pore K+ channel | KCNK1 | TWIK1 | 1q42-q43 | Brain, kidney, heart | Blocker: Ba2+, quinidine, quinine |
Lesage et al., 1996a
Lesage et al., 1996b Orias et al., 1997b | |
| KCNK2 | TREK | 1q41 | Brain, lung | Potentiated by arachidonic acid, riluzole, chloroform, lysophosphatidylcholine, diethyl ether, halothane, isoflurane |
Fink et al., 1996
Lesage and Lazdunski, 1998 Patel et al., 1999 Meadows et al., 2000 Duprat et al., 2000 Maingret et al., 2000 | ||
| KCNK3 | TASK | 2p23 | Heart, brain, pancreas, placenta | a. Sensitive to external pH b. Activated by halothane, isoflurane |
Duprat et al., 1997
Lesage and Lazdunski, 1998 Manjunath et al., 1999 Patel et al., 1999 | ||
| KCNK5 | TASK2 | 6p21 | Kidney | a. Sensitive to external pH b. Blocker: quinine, quinidine | Reyes et al., 1998 | ||
| KCNK6 | TWIK2, TOSS | 19q13.1 | Eyes, lung, stomach, embryo | Sensitive to internal pH |
Chavez et al., 1999
Gray et al., 1999 Pountney et al., 1999 Salinas et al., 1999 | ||
| KCNK7 | 11q13 | Salinas et al., 1999 | |||||
| TRAAK | 11q13 | Brain, spinal cord, retina | a. Blocker: gadolinium b. Opener: unsaturated fatty acid (arachidonic acid), riluzole, lysophosphatidylcholine c. Stretch-activated |
Duprat et al., 2000
Lesage et al., 2000 Maingret et al., 2000 | |||
| CTBAK-1 | Heart, brain, kidney | Blocker: Ba2+ | Kim et al., 1998 |
4-AP, 4-aminopyridine; AgTX2, angiotoxin 2; CTX, charybdotoxin; α-DTX, α-dendrotoxin; HgTX1, hongotoxin 1; IbTX, iberiotoxin; KTX, kaliotoxin; MgTX, margatoxin; NxTX, noxiustoxin; PaTX, phrixotoxin; ScTX, scyllatoxin.