Hippocampal GABA(A) channel conductance increased by diazepam

Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance.

Curmi, J P (författare)
Birnir, BryndisLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,John Curtin School of Medical Research, Australian National University(Swepub:uu)brybi979 (författare)
Gage, P W (författare)
Institutionen för kliniska vetenskaper, MalmöMedicinska fakulteten (creator_code:org_t)

Ingår i:Nature: Springer Science and Business Media LLC388:6637, s. 71-750028-08361476-4687

Av författaren/redakt...: Eghbali, M; Curmi, J P; Birnir, Bryndis; Gage, P W

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