The voltage-gated sodium channel Nav1.9 is required for inflammation-based urinary bladder dysfunction

• Published in: Neuroscience letters Vol. 452; no. 1; pp. 28 - 32
• Main Authors: Ritter, Amy M., Martin, William J., Thorneloe, Kevin S.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 06.03.2009; Elsevier
• Subjects: Acetic Acid - pharmacology; Animals; Antirheumatic Agents - therapeutic use; Bacterial diseases; Bacterial diseases of the urinary system; Biological and medical sciences; Bladder afferent; Cyclophosphamide; Cyclophosphamide - therapeutic use; Cystitis; Cystitis - chemically induced; Cystitis - genetics; Cystitis - physiopathology; Dinoprostone - pharmacology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; In Vitro Techniques; Infectious diseases; Inflammation; Male; Medical sciences; Mice; Mice, Knockout; NAV1.9 Voltage-Gated Sodium Channel; Nerve Fibers, Unmyelinated - drug effects; Nerve Fibers, Unmyelinated - physiology; Neuropeptides - deficiency; Neuropeptides - physiology; Prostaglandin E2; Sodium channel; Sodium Channel Blockers - pharmacology; Sodium Channels - deficiency; Sodium Channels - physiology; Tetrodotoxin - pharmacology; Urinary Bladder - drug effects; Urination - drug effects; Urodynamics - drug effects; Urodynamics - genetics; Vertebrates: nervous system and sense organs; Prostaglandin E2; Inflammation; Sodium channel; Bladder afferent; Cystitis; Urinary system disease; Arachidonic acid derivatives; Ionic channel; Urinary tract disease; Urinary system; Sodium; Urinary bladder; Eicosanoid; Bladder disease
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.12.051

Tetrodotoxin (TTX)-resistant sodium channels are found in small diameter primary sensory neurons and are thought to be important in the maintenance of inflammatory pain. Here we examined bladder urodynamics of Nav1.9 voltage-gated sodium channel knock out (KO) mice, and the contribution of Nav1.9 to the development of inflammation-based bladder dysfunction. Basal urodynamics were not different between wildtype (WT) mice and those lacking Nav1.9. Peripheral nerve recordings from pelvic afferents in Nav1.9 KO mice revealed a lack of sensitization to intravesicularly applied prostaglandin E2 (PGE2). Consistent with this, cyclophosphamide treatment in vivo, which is associated with an enhancement of PGE2 production, evoked a reduction in bladder capacity of WT, but not Nav1.9 KO mice. We conclude that the Nav1.9 sodium channel provides an important link between inflammatory processes and changes in urodynamic properties that occur during urinary bladder inflammation.