| 1. |
- Bhandage, Amol K., 1988-, et al.
(författare)
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Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 213:3, s. 575-585
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Tidskriftsartikel (refereegranskat)abstract
- AimThe concept of nerve-driven immunity recognizes a link between the nervous and the immune system. -aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain, and receptors activated by GABA can be expressed by immune cells. Here, we examined whether the expression of GABA receptors and chloride transporters in human peripheral blood mononuclear cells (PBMCs) was influenced by gender, pregnancy or mental health. MethodsWe used RT-qPCR to determine the mRNA expression level in PBMCs from men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15). ResultsThe 2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The and 2 subunits were up-regulated by pregnancy, whereas the epsilon subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in turn, commonly expressed the 6 and the 2 subunits. The 1 and epsilon subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women, while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs. ConclusionThe results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.
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| 2. |
- Dalziel, J E, et al.
(författare)
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A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors.
- 1999
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Ingår i: European Journal of Pharmacology. - 0014-2999 .- 1879-0712. ; 370:3, s. 345-8
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Tidskriftsartikel (refereegranskat)abstract
- Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.
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| 3. |
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| 4. |
- Tierney, M L, et al.
(författare)
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Two threonine residues in the M2 segment of the alpha 1 beta 1 GABAA receptor are critical for ion channel function.
- 1998
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Ingår i: Receptors and Channels. - 1060-6823 .- 1607-856X. ; 5:2, s. 113-24
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Tidskriftsartikel (refereegranskat)abstract
- The role of three threonine residues in the M2 hydrophobic region of the GABAA receptor has been investigated by replacing these polar residues with alanine at the 6', 10' and 13' positions of M2 in the GABAA alpha 1, and beta 1 subunits and co-expressing the mutated subunits in the baculovirus Sf9 insect cell system. GABA did not elicit a current in cells expressing either the 6' or 13' threonine to the alanine mutants. The mutant subunits formed intact heteromeric GABAA receptors as judged by the binding of [3H] muscimol or the relative level of alpha 1 protein present in the plasma membrane. In contrast, a chloride current was generated by GABA in cells expressing the 10' mutant receptor. However, the current decayed more rapidly to baseline in the continued presence of GABA in the 10' mutant receptor than in the wild type receptor. The results are discussed in terms of the possible roles of the threonine residues in the ion conduction pathway.
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| 5. |
- Birnir, Bryndis, et al.
(författare)
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A combination of human alpha 1 and beta 1 subunits is required for formation of detectable GABA-activated chloride channels in Sf9 cells.
- 1992
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 250:1329, s. 307-12
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Tidskriftsartikel (refereegranskat)abstract
- The baculovirus expression system was used to produce alpha 1 and beta 1 subunits of the human GABAA receptor in Sf9 cells. In cells infected with both alpha 1 and beta 1 recombinant viruses, GABA elicited an outwardly rectifying chloride current that was blocked by bicuculline and potentiated by pentobarbitone. GABA did not produce detectable currents in cells infected with either alpha 1 or beta 1 recombinant viruses alone. In these cells, and in control (non-infected) Sf9 cells, pentobarbitone depressed the leakage current (Ki = 55 microM). Fluorescently labelled monoclonal antibodies to the alpha 1 subunit showed greater amounts of the alpha 1 subunit in cells infected with only the alpha 1 recombinant virus than in cells co-infected with the alpha 1 and beta 1 recombinant viruses. Fluorescence of the plasma membrane was seen in cells co-infected with the alpha 1 and beta 1 recombinant viruses, but was absent in cells infected with only the alpha 1 recombinant virus. It was concluded that the alpha 1 subunit normally interacts with the beta 1 subunit to be transported to the plasma membrane in Sf9 cells.
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| 6. |
- Birnir, Bryndis, et al.
(författare)
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A structural determinant of desensitization and allosteric regulation by pentobarbitone of the GABAA receptor.
- 1997
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Ingår i: Journal of Membrane Biology. - 0022-2631 .- 1432-1424. ; 155:2, s. 157-66
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Tidskriftsartikel (refereegranskat)abstract
- Functional properties of the alpha1beta1 GABAA receptor changes in a subunit-specific manner when a threonine residue in the M2 region at the 12' position was mutated to glutamine. The rate and extent of desensitization increased in all mutants but the rate of activation was faster in the beta1 mutants. A negligible plateau current and abolition of potentiation by pentobarbitone of the GABA-activated current depended on the Thr 12' Gln mutation being present in the beta1 subunit. The Hill coefficient of the peak current response to GABA was reduced to less than one also in a beta1 subunit-specific manner. It was concluded that the beta1 subunit dominated conformational changes activated by GABA.
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| 7. |
- Birnir, Bryndis, et al.
(författare)
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Bicuculline, pentobarbital and diazepam modulate spontaneous GABA(A) channels in rat hippocampal neurons
- 2000
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 131:4, s. 695-704
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Tidskriftsartikel (refereegranskat)abstract
- Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (-Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 microM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 microM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. Application of 100 microM pentobarbital or 1 microM diazepam caused 2 - 4 fold increase in the maximum channel conductance of low conductance (<40 pS) spontaneously active channels. The observation of spontaneously opening GABA(A) channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics.
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| 8. |
- Birnir, Bryndis, et al.
(författare)
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Characteristics of GABAA channels in rat dentate gyrus.
- 1994
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Ingår i: Journal of Membrane Biology. - 0022-2631 .- 1432-1424. ; 142:1, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.
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| 9. |
- Birnir, Bryndis, et al.
(författare)
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Conductance of recombinant GABA(A) channels is increased in cells co-expressing GABA(A) receptor-associated protein
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 279:21, s. 21701-21706
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Tidskriftsartikel (refereegranskat)abstract
- High conductance gamma- aminobutyric acid type A ( GABA(A)) channels (> 40 picosiemens ( pS)) have been reported in some studies on GABA(A) channels in situ but not in others, whereas recombinant GABA(A) channels do not appear to display conductances above 40 pS. Furthermore, the conductance of some native GABA(A) channels can be increased by diazepam or pentobarbital, which are effects not reported for expressed GABA(A) channels. GABARAP, a protein associated with native GABA(A) channels, has been reported to cause clustering of GABA(A) receptors and changes in channel kinetics. We have recorded single channel currents activated by GABA in L929 cells expressing alpha(1), beta(1), and gamma(2S) subunits of human GABA(A) receptors. Channel conductance was never higher than 40 pS and was not significantly increased by diazepam or pentobarbital, although open probability was increased. In contrast, in cells expressing the same three subunits together with GABARAP, channel conductance could be significantly higher than 40 pS, and channel conductance was increased by diazepam and pentobarbital. GABARAP caused clustering of receptors in L929 cells, and we suggest that there may be interactions between subunits of clustered GABA(A) receptors that make them open co- operatively to give high conductance " channels." Recombinant channels may require the influence of GABARAP and perhaps other intracellular proteins to adopt a fuller repertoire of properties of native channels.
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| 10. |
- Birnir, B., et al.
(författare)
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Derivation of the viscous Moore-Greitzer equation for aeroengine flow
- 2007
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Ingår i: Journal of Mathematical Physics. - : AIP Publishing. - 0022-2488 .- 1089-7658. ; 48:6
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Tidskriftsartikel (refereegranskat)abstract
- The viscous Moore-Greitzer equation modeling the airflow through the compression system in turbomachines, such as a jet engine, is derived using a scaled Navier-Stokes equation. The method utilizes a separation of scale argument based on the different spatial scales in the engine and the different time scales in the flow. The pitch and size of the rotor-stator pair of blades provides a small parameter, which is the size of the local cell. The motion of the stator and rotor blades in the compressor produces a very turbulent flow on a fast time scale. The leading order equation, for the fast time and local scales, describes this turbulent flow. The next order equations produce an axisymmetric swirl and a flow pattern analogous to Rayleigh-B´nard convection rolls in Rayleigh-B´nard convection. On a much larger spatial scale and a slower time scale, there exist modulations of the flow including instabilities called surge and stall. A higher order equation, in the small parameter, describes these global flow modulations, when averaged over the small (local) spatial scales, the fast time scale, and the time scale of the vortex rotations. Thus a more general system of spatially global, slow time equations is obtained. This system can be solved numerically without any approximations. The viscous Moore-Greitzer equation is obtained when small inertial terms are dropped from these slow time, spatially global equations averaged once more in the axial direction. The new equations are simulated with two different simplifying assumptions and the results are compared with simulations of the viscous Moore-Greitzer equations. © 2007 American Institute of Physics.
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