Table 1.
Ion Channels in Pancreatic β-cells Involved in Insulin
| Family | Channel | Gene | Function in the β-cell | Activators | Blockers | References |
|---|---|---|---|---|---|---|
| Inward-rectifying K+ channels | Kir2.1 | Kcnj2/KCNJ2 | Spike repolarization? | Zacopride | ML133, Ba2+ | (221, 304, 305) |
| Kir3.2 (GIRK2) | Kcnj6 | Spike repolarization in response to hormones and neurotransmitters | Noradrenaline, somatostatin, galanin | Atomoxetine, Tertiapin, Ba2+ | (80, 144) | |
| Kir6.2/SUR1 (KATP) | Kcnj11/KCNJ11 Abcc8/ABCC8 | Mediates membrane potential and its coupling to metabolism | Diazoxide | Sulfonylureas, ATP/ADP ratio, glinides | (103, 163, 174) | |
| Voltage-gated Ca2+ channels | Cav1.2 (L-type) | Cacna1c/CACNA1C | Mediates Ca2+ influx during electrical activity | (S)-(-)-Bay K8644 | Dihydropyridines, benzothiazepines, phenylalkylamines | (153, 186, 251, 298) |
| Cav1.3 (L-type) | Cacna1d/CACNA1D | Mediates Ca2+ influx during electrical activity | (S)-(-)-Bay K8644 | Dihydropyridines, benzothiazepines, phenylalkylamines | (153, 186, 251, 298) | |
| Cav2.1 (P/Q-type) | Cacna1a/CACNA1A | Triggering exocytosis of insulin granules | – | ω-Agatoxin IVA | (36, 161) | |
| Cav2.2 (N-type) | Cacna1b/CACNA1B | Spiking? | – | ω-Conotoxin GVIA | (282) | |
| Cav2.3 (R-type) | Cacna1e | Spiking? | – | SNX482 | (188, 288) | |
| Cav3.1 (T-type) | Cacna1g/CACNA1G | Low threshold spiking | – | Amiloride, NiCl2, NNC55-3096 | (36, 154, 275, 282) | |
| Cav3.2 (T-Type) | Cacna1h/CACNA1H | Low threshold spiking | – | Amiloride, NiCl2, NNC55-3096 | (36, 154, 275, 282) | |
| Voltage-gated Na+ channels | Nav1.3 | Scn3a/SCN3A | Upstroke of action potential | Batrachotoxin, veratridine | Tetrodotoxin, saxitoxin | (18, 30, 36, 189) |
| Nav1.6 | Scn8a/SCN8A | Upstroke of action potential | Batrachotoxin, veratridine | Tetrodotoxin, saxitoxin | (18, 30, 36, 189) | |
| Nav1.7 | Scn9a/SCN9A | Upstroke of action potential | Batrachotoxin, veratridine | Tetrodotoxin, Saxitoxin | (18, 30, 36, 189) | |
| Volume-regulated Cl− channels | VRAC/SWELL1 | Lrrc8a/LRRC8A | Membrane depolarization and response to swelling; volume regulation | Cell swelling, cAMP | DCPIB, DIDS, NPPB, niflumic acid, glyburide | (131, 141) |
| Ca2+-activated Cl− channels | Anoctamin-1 | Ano1/ANO1 | Membrane depolarization | Ca2+ | T-AO1, tannic acid, niflumic acid | (61, 78, 204) |
| Anoctamin-2 | Ano2/ANO2 | Membrane depolarization | Ca2+ | T-AO1, tannic acid, niflumic acid | (61, 78, 204) | |
| Other Cl− channels | CFTR | ABCC7 | Acidification of insulin-containing granules | PKA phosphorylation | NPPB, niflumic acid | (65, 77) |
| Calcium-activated K+ (Kca) channels | BK (KCa1.1) | Kcnma1/KCNMA1 | Spike repolarization | Ca2+, membrane depolarization | Charybdotoxin, iberiotoxin, paxillin, TEA | (58, 116, 150, 187) |
| SK1 (KCa2.1) | Kcnn1/KCNN1 | Modulates Ca2+ oscillations, repolarization of the plateau potential | Ca2+, 1-EBIO, GW542573 | Apamin, UCL 1684 | (29, 112, 273, 307) | |
| SK2 (KCa2.2) | Kcnn2/KCNN2 | Modulates Ca2+ oscillations, repolarization of the plateau potential | Ca2+, 1-EBIO, CyPPA | Apamin, UCL 1684 | (29, 112, 273, 307) | |
| SK3 (KCa2.3) | Kcnn3/KCNN3 | Modulates Ca2+ oscillations, repolarization of the plateau potential | Ca2+, 1-EBIO, CyPPA | Apamin, UCL 1684 | (29, 112, 273, 307) | |
| SK4 (IK, KCa3.1) | Kcnn4/KCNN4 | Modulates Ca2+ oscillations, repolarization of the plateau potential | Ca2+, 1-EBIO, SKA-111 | TRAM-34 | (29, 72, 112, 273, 307) | |
| Voltage-dependent K+ channels | Kv2.1 | Kcnb1/KCNB1 | Spike repolarization | – | TEA, quinidine, aminopyridines, and dendrotoxin | (32, 117, 164, 222) |
| TRP channels | TRPC1 | Trpc1/TRPC1 | Mediation of store-operated Ca2+ channels | – | La3+, Gd3+, 2-APB | (166, 234, 267, 311) |
| TRPC3 | Trpc3 | β-Cell development and GPR40-induced membrane depolarization | GSK1702934A, artemisinin | Pyr3 | (143, 287, 300) | |
| TRPC4 | Trpc4 | KATP trafficking | leptin, (−)-englerin | M084, ML204 | (3, 181, 257, 264) | |
| TRPM2 | Trpm2/TRPM2 | Mediates Ca2+ influx induced by glucose and GLP-1 | Ca2+, Adenosine 5′-diphosphate ribose, forskolin, exendin-4 | N-(p-amylcinnamoyl) anthranilic acid, curcumin, JNJ-28583113 | (17, 82, 138, 172, 201, 280, 283) | |
| TRPM5 | Trpm5/TRPM5 | Mediates glucose-induced oscillation | Arachidonic acid, steviol glycoside, GLP-1 | Flufenamic acid, TPPO | (55, 200, 209, 259, 286) | |
| TRPV2 | Trpv2 | Membrane depolarization | Cell swelling, cannabidiol | SET2 | (51, 215, 246) | |
| Two-pore-domain K+ channels | TALK1 | Knck16/KNCK16 | Resting “leak” conductance | pH (alkaline), nitric oxide | pH (acidic) | (74, 132, 291) |
| TASK1 | Kcnk3/KCNK3 | Resting “leak” conductance | pH (alkaline) | pH (acidic), A1899, ML365 | (63, 74, 292) |