5-HT potentiation of the GABA_A response in the rat sacral dorsal commissural neurones

Abstract

1. The modulatory effect of 5-hydroxytryptamine (5-HT) on the γ-aminobutyric acid_A (GABA_A) response was investigated in the neurones freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions.

2. 5-HT potentiated GABA-induced Cl⁻ current (I_GABA) without affecting the reversal potential of I_GABA and the apparent affinity of GABA to its receptor.

3. α-Methyl-5-HT mimicked the potentiation effect of 5-HT on I_GABA while ketanserine blocked it. 1-Oleoyl-2-acetyl-glycerol (OAG) potentiated I_GABA, and the effect of 5-HT on I_GABA was occluded by OAG pretreatment. In the presence of chelerythrine, 5-HT failed to potentiate I_GABA, suggesting that protein kinase C (PKC) is involved in the pathway through which the activation of the 5-HT₂ receptor potentiates the I_GABA.

4. The facilitatory effect of 5-HT on I_GABA remained in the presence of BAPTA-AM. LiCl also had no effect on 5-HT-induced potentiation of I_GABA.

5. H-89, genistein, okadaic acid and pervanadate all had no effects on 5-HT potentiation of I_GABA. Pertussis toxin treatment for 6–8 h did not block the facilitatory effect of 5-HT on I_GABA.

6. The present results show that GABA_A receptor in the rat SDCN could be modulated in situ by 5-HT, one of the major transmitters involved in the supraspinal control of nociception, and that the phosphorylation of GABA_A receptor by PKC may be sufficient to support such modulation. The results also strongly support the hypothesis that the cotransmission by 5-HT and GABA has an important role in the spinal cord.

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