Different pharmacological profile in alpha1-gamma2 and alpha1-beta2-gamma2 GABAA receptors

• Autorzy: Brodzki M. , Czyzewska M.M. , Rutkowski R. , Kisiel M. , Jatczak M. , Mozrzymas J.W.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: GABAA receptors (GABAAR) mediate the main component of ionotropic inhibitory transmission in adult mammalian brain. These receptors are heteropentamers and are strongly diversified throughout the CNS but the most frequent subunit composition is alpha1-beta2-gamma2. It has been reported that alpha1-gamma2 receptors can be potently expressed in recombinant GABAAR model (Verdoorn et al. 1990). In this study we aimed to characterize the kinetic and pharmacological profile of these receptors in comparison to alpha1-beta2-gamma2 ones. METHODS: We used patch-clamp technique with ultrafast (~10e–4 s) solution exchange based on theta-glass capillaries driven by a piezoelectric translator. We used HEK293 cells which were transiently transfected by GABAAR subunit cDNA using standard calcium phosphate method. Modulators used were zinc ions, low extracellular pH, flurazepam and pentobarbital. RESULTS: Zinc ions inhibited current responses more strongly for alpha1-gamma2 GABAARs, however, zinc effect on desensitization onset was observed only for alpha1-beta2-gamma2 receptors. In the case of responses mediated by alpha1-beta2-gamma2 receptors, lowering extracellular pH enhanced current amplitudes and prolonged deactivation time course of currents elicited by short and saturating GABA pulses to a much larger extent than for alpha1-gamma2 ones. Saturating GABA elicited responses mediated by alpha1-beta2-gamma2 receptors were slightly inhibited by flurazepam, whereas in the case of alpha1-gamma2 receptors, currents were significantly potentiated. Activation by high concentrations of pentobarbital yielded similar rebound current amplitudes in both receptor subtypes. CONCLUSIONS: We found that although alpha1-gamma2 receptors show a similar kinetic profile to alpha1-beta2-gamma2 receptors they are characterized by pharmacological properties that are substantially different. Supported by NCN grant DEC-2013/11/B/NZ3/00983.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S46

Twórcy

autor

Brodzki M.

• Laboratory of Cellular Neurobiology, Department of Animal Molecular Physiology, University of Wroclaw, Wroclaw, Poland
• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Czyzewska M.M.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Rutkowski R.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Kisiel M.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Jatczak M.

• Laboratory of Cellular Neurobiology, Department of Animal Molecular Physiology, University of Wroclaw, Wroclaw, Poland
• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Mozrzymas J.W.

• Laboratory of Cellular Neurobiology, Department of Animal Molecular Physiology, University of Wroclaw, Wroclaw, Poland
• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland