KCC2-deficient mice show reduced sensitivity to diazepam, but normal alcohol-induced motor impairment, gaboxadol-induced sedation, and neurosteroid-induced hypnosis

Neuropsychopharmacology

Volumn 32, Issue 4, 2007, Pages 911-918

  Tornberg, Janne ^a   Segerstråle, Mikael ^a   Kulesskaya, Natalia ^a   Voikar, Vootele ^a   Taira, Tomi ^a   Airaksinen, Matti S ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Benzodiazepine; Chloride homeostasis; GABAA receptor; Gramicidin perforated patch recording; Shunting; Slc12a5; Tonic

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALCOHOL; COTRANSPORTER; DIAZEPAM; GABOXADOL; NEUROSTEROID; POTASSIUM CHLORIDE COTRANSPORTER KCC2; UNCLASSIFIED DRUG;

ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BRAIN ELECTROPHYSIOLOGY; BRAIN LEVEL; CONTROLLED STUDY; FEMALE; GABAERGIC SYSTEM; GABAERGIC TRANSMISSION; HYPERPOLARIZATION; HYPNOSIS; INHIBITION KINETICS; KNOCKOUT MOUSE; MALE; MOTOR DYSFUNCTION; MOUSE; NEUROPHYSIOLOGY; NONHUMAN; PRIORITY JOURNAL; RECEPTOR INTRINSIC ACTIVITY; SEDATION;

ACTION POTENTIALS; ANIMALS; ANTICONVULSANTS; BEHAVIOR, ANIMAL; CENTRAL NERVOUS SYSTEM DEPRESSANTS; DIAZEPAM; ETHANOL; EXPLORATORY BEHAVIOR; HIPPOCAMPUS; IMMOBILITY RESPONSE, TONIC; ISOXAZOLES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MOTOR SKILLS DISORDERS; NEURONS; SYMPORTERS;

EID: 33947237851     PISSN: 0893133X     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.npp.1301195     Document Type: Article

References (41)

1. Bai D, Zhu G, Pennefather P, Jackson MF, MacDonald JF, Orser BA (2001). Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons. Mol Pharmacol 59: 814-824.
2. Belelli D, Peden DR, Rosahl TW, Wafford KA, Lambert JJ (2005). Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics. J Neurosci 25: 11513-11520.
3. Bieda MC, MacIver MB (2004). Major role for tonic GABAA conductances in anesthetic suppression of intrinsic neuronal excitability. J Neurophysiol 92: 1658-1667.
4. Borghese CM, Storustovu SI, Ebert B, Herd MB, Belelli D, Lambert JJ et al (2006). The delta subunit of γ-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol. J Pharmacol Exp Ther 316: 1360-1368.
5. Brickley SG, Cull-Candy SG, Farrant M (1996). Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol London 497: 753-759.
6. Brown N, Kerby J, Bonnert TP, Whiting PJ, Wafford KA (2002). Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors. Br J Pharmacol 136: 965-974.
7. Cope DW, Hughes SW, Crunelli V (2005). GABAA receptormediated tonic inhibition in thalamic neurons. J Neurosci 25: 11553-11563.
8. Chadderton P, Margrie TW, Hausser M (2004). Integration of quanta in cerebellar granule cells during sensory processing. Nature 428: 856-860.
9. Crestani F, Martin JR, Mohler H, Rudolph U (2000). Resolving differences in GABAA receptor mutant mouse studies. Nat Neurosci 3: 1059-1059.
10. Farrant M, Nusser Z (2005). Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6: 215-229.
11. Hamann M, Rossi DJ, Attwell D (2002). Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33: 625-633.
12. Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M (2005). Alcohol-induced motor impairment caused by increased extra-synaptic GABA(A) receptor activity. Nat Neurosci 8: 339-345.
13. Hanchar HJ, Chutsrinopkun P, Meera P, Supavilai P, Sieghart W, Wallner M et al (2006). Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to α4/6β3δ GABAA receptors. Proc Natl Acad Sci USA 103: 8546-8551.
14. Hevers W, Luddens H (1998). The diversity of GABA(A) receptors - pharmacological and electrophysiological properties of GABA(A) channel subtypes. Mol Neurobiol 18: 35-86.
15. Hubner CA, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch TJ (2001). Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron 30: 515-524.
16. Koch C, Poggio T, Torre V (1983). Nonlinear interactions in a dendritic tree: localization, timing, and role in information processing. Proc Natl Acad Sci USA 80: 2799-2802.
17. A receptor subtypes as targets for neuropsychiatric drug development. Pharmacol Ther 109: 12-32.
18. Maguire JL, Stell BM, Rafizadeh M, Mody I (2005). Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci 8: 797-804.
19. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR et al (2000). Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor (alpha)1 subtype. Nat Neurosci 3: 587-592.
20. Mercado A, Mount DB, Gamba G (2004). Electroneutral cation-chloride cotransporters in the central nervous system. Neurochem Res 29: 17-25.
21. Mihalek RM, Banerjee PK, Korpi ER, Quinlan JJ, Firestone LL, Mi ZP et al (1999). Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci USA 96: 12905-12910.
22. Mitchell SJ, Silver RA (2003). Shunting inhibition modulates neuronal gain during synaptic excitation. Neuron 38: 433-445.
23. Mody I, Pearce RA (2004). Diversity of inhibitory neurotransmission through GABAA receptors. Trends Neurosci 27: 569-575.
24. Nusser Z, Sieghart W, Somogyi P (1998). Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J Neurosci 18: 1693-1703.
25. Owens DF, Kriegstein AR (2002). Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3: 715-727.
26. Payne JA, Rivera C, Voipio J, Kaila K (2003). Cation-chloride co-transporters in neuronal communication, development and trauma. Trends Neurosci 26: 199-206.
27. - co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397: 251-255.
28. Rudolph U, Mohler H (2004). Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol 44: 475-498.
29. Rudolph U, Crestani F, Benke D, Brunig I, Benson JA, Fritschy JM et al (1999). Benzodiazepine actions mediated by specific γ-aminobutyric acid A receptor subtypes. Nature 401: 796-800.
30. Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC (2005). Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 25: 10016-10024.
31. Semyanov A, Walker MC, Kullmann DM, Silver RA (2004). Tonically active GABAA receptors: modulating gain and maintaining the tone. Trends Neurosci 27: 262-269.
32. Sieghart W, Speck G (2002). Subunit composition, distribution and function of GABAA receptor subtypes. Curr Top Med Chem 2: 795-816.
33. Staley KJ, Mody I (1992). Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptormediated postsynaptic conductance. J Neurophysiol 68: 197-212.
34. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I (2003). Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc Natl Acad Sci USA 100: 14439-14444.
35. Tornberg J, Voikar V, Savilahti H, Rauvala H, Airaksinen MS (2005). Behavioural phenotypes of hypomorphic KCC2-deficient mice. Eur J Neurosci 21: 1327-1337.
36. Wallner M, Hanchar HJ, Olsen RW (2003). Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc Natl Acad Sci USA 100: 15218-15223.
37. A receptors are reversed by the behavioral alcohol antagonist Ro15-4513. Proc Natl Acad Sci USA 103: 8540-8545.
38. Wei W, Faria LC, Mody I (2004). Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABAA receptors in hippocampal neurons. J Neurosci 24: 8379-8382.
39. Wohlfarth KM, Bianchi MT, Macdonald RL (2002). Enhanced neurosteroid potentiation of ternary GABAA receptors containing the delta subunit. J Neurosci 22: 1541-1549.
40. Woo NS, Lu JM, England R, McClellan R, Dufour S, Mount DB et al (2002). Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene. Hippocampus 12: 258-268.
41. Zhu L, Lovinger D, Delpire E (2005). Cortical neurons lacking KCC2 expression show impaired regulation of intracellular chloride. J Neurophysiol 93: 1557-1568.