Blockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus

doi:10.1016/0014-2999(91)90467-5

European Journal of Pharmacology

Volume 199, Issue 2, 25 June 1991, Pages 259-262

https://doi.org/10.1016/0014-2999(91)90467-5 Get rights and content

Abstract

Intracellular injection of QX-314 blocked the ability of baclofen and 5-carboxyamidotryptamine to hyperpolarize cells in the rat hippocampus. This effect was not associated with a reduction in the effects of norepinephrine on these cells nor a blockade of the potassium channels underlying the calcium-dependent afterhyperpolarization responsible or significant changes in membrane potential. These results suggest that QX-314 is an effective blocker of G-protein-gated potassium channels in this region.

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All experiments were performed using a high-chloride intracellular solution: 140 mM CsCl, 10 mM HEPES, 10 ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 1 mM CaCl2, 2 mM Mg-Adenosine triphosphate (ATP), .2 mM Mg-Guanosine triphosphate (GTP), and 5 mM QX-314 in order to enhance the detection of GABAA receptor mediated currents. QX-314 and Cs+ were used to suppress the effects of postsynaptic GABAB receptors by blocking potassium channels.3,66,77 Tetrodotoxin (.5 µM, Sigma-Aldrich, St. Louis, MO), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 µM; Sigma-Aldrich), gabazine (10 µM, Tocris Bioscience, Bristol, United Kingdom), R(+)-baclofen (10 µM, Sigma-Aldrich), and carbachol (2 µM, Sigma-Aldrich) were dissolved in distilled water (dH2O).
Pain after spinal cord injury (SCI-Pain) is one of the most debilitating sequelae of spinal cord injury, characterized as relentless, excruciating pain that is largely refractory to treatments. Although it is generally agreed that SCI-Pain results from maladaptive plasticity in the pain processing pathway that includes the spinothalamic tract and somatosensory thalamus, the specific mechanisms underlying the development and maintenance of such pain are yet unclear. However, accumulating evidence suggests that SCI-Pain may be causally related to abnormal thalamic disinhibition, leading to hyperactivity in the posterior thalamic nucleus (PO), a higher-order nucleus involved in somatosensory and pain processing. We previously described several presynaptic mechanisms by which activity in PO is regulated, including the regulation of GABAergic as well as glutamatergic release by presynaptic metabotropic gamma-aminobutyric acid (GABA_B) receptors. Using acute slices from a mouse model of SCI-Pain, we tested whether such mechanisms are affected by SCI-Pain. We reveal 2 abnormal changes in presynaptic signaling in the SCI-Pain condition. The substantial tonic activation of presynaptic GABA_B receptors on GABAergic projections to PO—characteristic of normal animals—was absent in mice with SCI-Pain. Also absent in mice with SCI-Pain was the normal presynaptic regulation of glutamatergic projections to the PO by GABA_B receptors. The loss of these regulatory presynaptic mechanisms in SCI-Pain may be an element of maladaptive plasticity leading to PO hyperexcitability and behavioral pain, and may suggest targets for development of novel treatments.
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The internal solution contained (in mM): CsCl 43; CsMeSO4 92; TEA 5; EGTA 2; MgCl2 1; Hepes 10; QX314 3 and Mg–ATP 4. The inclusion of QX314 blocked the voltage-dependent sodium channels and GABAB receptor activated potassium conductance (Andrade, 1991). The pipette resistance was 2–4 MΩ using this internal solution.
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Short communicationBlockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus

Abstract

Biochim. Biophys. Acta

Neurosci. Lett.

A G-protein couples serotonin and GABAB receptors to the same channels in hippocampus

Science

Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro

J. Physiol.

Short communication
Blockade of neurotransmitter-activated K⁺ conductance by QX-314 in the rat hippocampus

A G-protein couples serotonin and GABA_B receptors to the same channels in hippocampus