Table 1.
Plasticity of neuronal GIRK channel activity
| Stimulus | Brain Region/Neuron | Plasticity | Mechanism | Refs. |
|---|---|---|---|---|
| Neuronal activity | ||||
| NMDAR activation | HPC culture | ↑ A1R-GIRK, GABABR-GIRK | Dephosphorylation/GIRK2 surface trafficking | (121, 125) |
| HFS | HPC slice culture | ↑ GABABR-GIRK | NMDAR, Ca2+/CaMKII | (186) |
| Burst/depolarization | VTA/dopamine | ↑ GABABR-GIRK, D2R-GIRK | NMDAR, Ca2+/CaMKII, GIRK3 | (73) |
| Tonic/LFS | VTA/dopamine | ↓ GABABR-GIRK | NMDAR, GIRK3 | |
| Drugs of abuse | ||||
| Cocaine | ||||
| Single injection | VTA/dopamine | ↓ GABABR-GIRK, D2R-GIRK | Internalization, D2/3 R-dependent | (187) |
| Repeated injection | VTA/dopamine | ↓ GABABR-GIRK | ||
| Single injection | VTA/GABA | ↓ GABABR-GIRK | (188) | |
| VTA/dopamine | - GABABR-GIRK | |||
| Repeated injection | PL/layer 5/6 pyramidal | ↓ GABABR-GIRK | Dephosphorylation/GABABR2 internalization | (39) |
| D1/5R-dependent | ||||
| PL/layer 2/3 pyramidal | - GABABR-GIRK | |||
| IL/layer 5/6 pyramidal | - GABABR-GIRK | |||
| Repeated injection | PL/GABA | - GABABR-GIRK | (189) | |
| Methamphetamine | ||||
| Single injection | VTA/GABA | ↓ GABABR-GIRK | Dephosphorylation/GABABR2 internalization | (188) |
| VTA/dopamine | ↓ GABABR-GIRK | |||
| Single injection | VTA/GABA | ↓ GABABR-GIRK | Dephosphorylation/GABABR2 | (74) |
| Repeated injection | VTA/dopamine | ↓ GABABR-GIRK, - D2R-GIRK | GIRK3, D1R/D2R-dependent | |
| Self-administration | Midbrain/dopamine | ↓ GABABR-GIRK, D2R-GIRK | Ca2+ | (190) |
| Repeated injection | VTA/dopamine | ↓ D2R-GIRK | ||
| Opioids | ||||
| Morphine | HPC culture | ↑ 5HT1AR-GIRK ↓ GABABR-GIRK | ↑ GIRK2, Ca2+/CaMKII, trafficking | (65, 191) |
| Remifentanil | PL/layer 5/6 pyramidal | ↓ GABABR-GIRK | (192) | |
| Ethanol | ||||
| Repeated injection | VTA/dopamine | ↑ D2R-GIRK, - GABABR-GIRK | (193) | |
| CIE/ethanol vapor | lateral OFC/pyramidal | ↓ GPCR-GIRK, ML297-GIRK | (194) | |
| Aversive experience | ||||
| Forced swim | DRN/serotonin | ↓ KOR-GIRK | p38 MAPK, GIRK1(Y12) | (195) |
| Foot-shock | LHb | ↓ GABABR-GIRK | PP2A dephosphorylation internalization | (196) |
| Predator odor | LHb | ↓ GABABR-GIRK | ||
| Restraint | LHb | ↓ GABABR-GIRK | ||
| Foot-shock | LHb | ↓ GABABR-GIRK | ||
| CUS | PL/layer 5/6 pyramidal | ↓ GABABR-GIRK, ML297-GIRK | ||
| Amyloid beta (Aβ) | ||||
| Aβ25–35 | HPC/CA3 pyramidal | ↓ GABABR-GIRK | ↓ GIRK expression | (197, 198) |
| Aβ1–42 | HPC culture | ↑ GABABR-GIRK | NMDAR, trafficking, p75NTR | (199) |
Examples of neuronal GIRK channel plasticity provoked by various stimuli in rodent models. CUS, chronic unpredictable stress; DRN, dorsal raphe nucleus; GABA, γ-aminobutyric acid; GIRK, G protein-gated inwardly rectifying K+; HFS, high-frequency stimulation; HPC, hippocampus; KOR, kappa opioid receptor; LFS, low-frequency stimulation; LHb, lateral habenula; MAPK, mitogen-activated protein kinase; NMDAR, N-methyl-d-aspartate receptor; OFC, orbitofrontal; PL, prelimbic; VTA, ventral tegmental area. Directional arrows, direction of plasticity: up arrows, strengthening; down arrows, weakening.