Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro

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Abstract
The role of inhibition in control of plateau‐generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. Blockade of γ‐aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10‐50 μM) and strychnine (5‐20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. Activation of GABAB receptors also inhibited plateau‐generating neurones. The selective agonist baclofen (5‐50 μM) inhibited wind‐up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2‐hydroxysaclofen (2‐OH‐saclofen, 100‐400 μM). Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1‐2 mM). When the baclofen‐induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind‐up and after‐discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2‐OH‐saclofen. The inhibition of plateau properties was observed even when the baclofen‐induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25‐0.5 μM). The baclofen‐sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L‐type Ca2+ channels. We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind‐up and after‐discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain.