45 L-methioninol, a TREK-1 channel blocker, induced a significant increase in premature contractions during the filling phase in sham operated mice. However, L-methioninol had no significant effect in obstructed mice, which showed an overactive detrusor phenotype. These results demonstrated that downregulation of TREK-1 channel in detrusor myocytes is associated

with OAB in a murine model of BOO.45 Ferroptosis targets Stabilizing membrane potential and reducing excitability of nerves and muscle cells are important functions of K+ channel.46 Several studies have reported on the relationship between OAB and K+ channel.47–51 Several modulators of these K+channels have been developed as potential treatment of OAB.52–54 Kita et al. investigated the effects of BOO on the expression and function of large conductance (BK) and small conductance (SK) Ca2+-activated K+ channels in detrusor smooth muscle in rats with 6-week BOO.55 The expression of the BK channel β1-subunit and the SK3 channel was FK228 remarkably increased in obstructed bladders. However, the expression of the BK channel β4-subunit was decreased as the severity of BOO-induced OAB progressed. These results advocate that long-term exposure to BOO for 6 weeks augments the function of both BK and SK types of Ca 2+-activated K+ channels in the detrusor

smooth muscle to induce an inhibition of bladder contractility, which might be a compensatory mechanism to reduce BOO-induced OAB.55 Molecular motor Activation of muscarinic receptors on the detrusor is one of the mechanisms of detrusor contraction. In addition, evidence showed that urothelial cells express muscarinic receptors,56 and that urothelial/suburothelial muscarinic receptors play a role in the etiology of OAB or sensory urgency.57,58 The P2X receptor is an ATP-gated ion channel that is probably composed of three protein subunits.59,60 ATP, released by stretched urothelial cells, acts on P2X3 receptors on suburothelial sensory afferents.61,62 Intravesical instillation of ATP induces OAB in conscious freely moving rats, further supporting a role for ATP in urothelial

signaling. A previous study on immunofluorescence staining showed that muscarinic and purinergic receptors were co-localized in both the urothelium and the muscle layer.63 Immunoreactivity and Western blotting showed that the expression of M2, M3 and P2X3 receptors was increased in the urothelium of BOO rats. Also, there was increased M3 receptor expression in the muscle layer of the BOO group.63 These results proposed that changes in urothelium receptor expression could have a role in mediating the afferent sensory responses in the urinary bladder.63 The prevalence of metabolic syndrome in the adult population is approximately 23%.64 Both OAB and metabolic syndrome have high prevalence in the population and affect public health profoundly.