Trifluoperazine blocks GABA-gated chloride currents in cultured chick spinal cord neurons

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Abstract

The effects of trifluoperazine (TFP) on γ-aminobutyric acid- (GABA) gated chloride currents were investigated using cultured chick embryonic spinal cord neurons (SCN) and gigaseal patch clamp recording techniques. TFP showed a dose-dependent attenuation of GABA responses with half-maximal block near 9 μM. The GABA antagonism was noncompetitive and voltage dependent with greater block at hyperpolarized potentials. At 10 μM, GABA induced little desensitization in response to prolonged applications in the absence of TFP. At 100 μM, GABA responses desensitized with a time constant near 27 s. Coapplication of TFP did not alter the lack of desensitization to 10 μM GABA but revealed a second, faster component (time constant ~ 0.7 s) to the attenuation at 100 μM GABA. Steady-state fluctuation analysis of the macroscopic GABA-gated current gave a power spectrum that was described by a simple Lorentzian function. The corner frequency of fluctuations to GABA [34.6 ± 7.3 (SE) Hz] remained unchanged during simultaneous application of GABA and TFP (33.0 ± 8.5 Hz), indicating that TFP does not alter the average GABA channel open duration. Single-channel recording from isolated outside-out membrane patches showed GABA-gated chloride events with a primary conductance of 26 pS and a minor component (representing < 5% of all events) of 10 pS. With simultaneous application of GABA and TFP, event amplitudes remained unchanged but the frequency of opening was decreased. The distribution of the main conductance channel open times were well described by the sum of two exponentials with time constants of 0.82 ± 0.18 and 7.4 ± 2.0 ms. These time constants were not significantly altered by 50 μM TFP. TFP, at 100 μM, attenuated responses to (% of control): GABA (7.5 ± 2.3), glycine (15.4 ± 5.5), and glutamate (64.5 ± 5.5). The proconvulsant tendency of TFP, in part, may be due to the greater block of responses to inhibitory than to excitatory transmitters.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalJournal of neurophysiology
Volume61
Issue number2
DOIs
StatePublished - Jan 1 1989

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