Presynaptic large‐conductance calcium‐activated potassium channels modulate GABAergic inhibitory synaptic transmission in the superficial dorsal horn of the mouse

Abstract

Large‐conductance calcium‐dependent potassium (BK) channels are found in various tissues, including nerve, smooth and skeletal muscles, and other cell types. They are potassium‐selective ion channels that are activated in response to increased intracellular calcium concentrations and transmembrane voltages.We previously reported that the BK channels that are located in presynaptic terminals control excitatory synaptic transmission in the superficial dorsal horn (SDH), and that functional downregulation of BK channels accompanies the neuropathic pain induced by peripheral nerve injury.In the present experiments, we attempted to clarify the physiological significance of BK channels in the modulation of GABAergic inhibitory synaptic transmission in the SDH where nociceptive information is processed.Spontaneously occurring GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded from the GFP‐negative neurons located in the SDH of a mouse spinal cord slice by using slice preparations from adult glutamate decarboxylase 67‐green fluorescent protein (GAD67‐GFP) knock‐in mice, and the effects of Iberiotoxin, a BK channel blocker, on the GABAergic mIPSCs were analyzed.Iberiotoxin increased the frequency of GABAergic mIPSCs without affecting the amplitude of GABAergic mIPSCs, suggesting that the activation of BK channels attenuates GABAergic synaptic transmission via presynaptic mechanisms.In order to clarify the role of BK channels in the nociceptive information processing which is modulated by GABAergic transmission, we are currently doing the similar experiments using peripheral nerve‐ligated neuropathic mice.Those results may provide clues for the underlying mechanisms of the nociceptive actions of BK channels in the SDH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.