Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

Figure 3

Electrophysiological conversion of chloride-dependent inhibitory synapses in the CNS. Neuropathologies arising from aberrant chloride homeostasis (i.e., chloride-opathies) can be mapped onto a graph of the Conversion Factor, 𝐶_𝐹, versus Δ^𝜇. 𝐶_𝐹 is a scaling factor for synaptic response. Aberrant chloride current is scaled to the synaptic chloride current under normal conditions (i.e., Δ^𝜇=0). The graph illustrates the special case of (8) where the resting membrane potential is unchanged in the cell with altered chloride driving potential (i.e., Δ^𝑉=0). Downregulation of Potassium Chloride Cotransporter (KCC2) leads to an increase in intracellular chloride. Hyperpolarizing GABAergic and glycinergic synapses become depolarizing synapses when 𝐸^∗_Cl becomes more positive than 𝑉_𝑚.