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.

Figure 2 Pathophysiology of fibromyalgia. Neuronal excitability due to amplified and altered central nervous system functioning linked to peripheral generators is associated with central sensitization. The central sensitization reflects the altered biochemistry and neurotransmitter levels. Up arrow: Raised levels relative to healthy subjects; Down arrow: Lowered levels relative to healthy subjects; CFS: Cerebrospinal fluid.