Kv7 channels a potential therapeutic target in fibromyalgia: A hypothesis

Figure 1 Schematic of a Kv7. 2 subunit with activators flupirtine and retigabine. Flupirtine and retigabine activate Kv7.2/7.3 channel complexes resulting in efflux of K⁺ leading to hyperpolarization and concomitant decrease in the resting membrane potential. Kv7.2/7.3 channel complexes are inhibited due to the release of calcium from the endoplasmic reticulum and the activation of M1-type muscarinic receptors by acetylcholine. Excessive levels of glutamate activating N-methyl-D-aspartic acid receptors which leads to an influx of Ca²⁺ ions into neurones is indirectly antagonised by the retigabine- or flupirtine-induced hyperpolarization suppressing free intracellular Ca²⁺ ion levels reducing neuronal excitability. AKAP: A-kinase anchoring protein; CaM: Calmodulin; NMDAR: N-methyl-D-aspartic acid receptor; PKC: Protein kinase C; PLCβ: Phospholipase C.