Volume 6, Number 3, 307-323, DOI: 10.1007/BF00711116

Diazepam action onγ-aminobutyric acid-activated chloride currents in internally perfused frog sensory neurons

Kiichi Hattori, Yutaka Oomura and Norio Akaike

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Abstract

1.  The Cl current (I Cl) ingamma-aminobutyric acid (GABA)-sensitive frog sensory neuron was separated from other Na+, Ca2+, and K+ currents using a suction pipette technique which allows internal perfusion under a single-electrode voltage clamp.
2.  Diazepam (DZP) itself evoked no response but facilitated the dose- and time-dependently GABA-inducedI Cl without changing the GABA equilibrium potential (E GABA) at concentrations ranging widely, from 3 × 10–9 to 10–4 M.
3.  In the presence of DZP, the GABA dose-response curve shifted to the left without changing the maximum current, indicating that DZP modifies the interaction between GABA and its receptor rather than affecting directly the channel activation step.
4.  The enhancement of the GABA-inducedI Cl by DZP depended neither on the membrane voltage nor on the inward or outward direction of theI Cl.
5.  DZP also potentiated theI Cl elicited by GABA agonists such asbeta-alanine, taurine, homotaurine, 5-aminovaleric acid,l-GABOB,d-GABOB, glycine, and muscimol.
6.  The GABA response enhanced by pentobarbital (PB) was further enhanced by adding DZP, indicating that DZP and PB do not act in the same way.
7.  Ro5-3663, a diazepam analogue, enhanced the GABA-inducedI Cl only in a narrow range of the concentrations but inhibited the current at concentrations higher than 2 × 10–6 M.

Key words  frog sensory neuron - internal perfusion - diazepam -  gamma-aminobutyric acid (GABA) - chloride current - facilitation

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