Role of bicarbonate ion in mediating decreased synaptic conductance in benzodiazepine tolerant hippocampal CA1 pyramidal neurons.
Brain Res
; 868(2): 202-14, 2000 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-10854572
ABSTRACT
Chronic flurazepam treatment substantially impairs the function of GABAergic synapses on hippocampal CA1 pyramidal cells. Previous findings included a significant decrease in the synaptic and unitary conductance of CA1 pyramidal neuron GABA(A) receptor channels and the appearance of a GABA(A)-receptor mediated depolarizing potential. To investigate the ionic basis of the decreased conductance, whole-cell voltage-clamp techniques were used to record evoked, GABA(A) receptor-mediated IPSCs carried by HCO(3)(-)-Cl(-) or Cl(-) alone. Hippocampal slices were prepared from rats administered flurazepam orally for 1 week, 2 days after ending drug treatment. Slices were superfused with HCO(3)(-)-aCSF or with HEPES-aCSF (without HCO(3)(-)) plus 50 microM APV and 10 microM DNQX. The micropipette contained 130 mM CsCl and 1 microM QX-314. GABA(A) receptors located on pyramidal cell somata or dendrites were activated monosynaptically by maximal stimulation of GABAergic terminals at the stratum oriens-pyramidale (SO-SP) or stratum lacunosum-molecular (S-L-M) border, respectively. In HCO(3)(-)-aCSF, there was a significant reduction in synaptic-conductance in flurazepam-treated neurons following both SO-SP (control 1058 pS, flurazepam 226 pS, P<0.01) and S-L-M (control 998 pS, flurazepam 179 pS, P<0.01) stimulation, as well as the total charge transfer, indicating a decreased HCO(3)(-)-Cl(-) flux. In HEPES-aCSF, the synaptic conductance and total charge transfer, and thus Cl(-) flux, was unchanged in flurazepam-treated neurons (SO-SP control 588 pS, flurazepam 580 pS, P>0.05; S-L-M control 595 pS, flurazepam 527 pS, P>0.05). Taken together, these findings suggest that a reduction in HCO(3)(-) flux may play a prominent role in mediating the action of GABA and that a loss of HCO(3)(-) conductance may significantly contribute to impaired GABA(A) receptor function after chronic benzodiazepine treatment.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzodiazepinas
/
Bicarbonatos
/
Células Piramidais
/
Receptores de GABA-A
/
Transmissão Sináptica
/
Tolerância a Medicamentos
/
Hipocampo
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article