The voltage-gated sodium channel Nav1.9 is required for inflammation-based urinary bladder dysfunction.
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.
Ritter
Amy M
AM
Department of Immunology, Merck Research Labs, Rahway, NJ 06070, United States. a_m_ritter@hotmail.com
Martin
William J
WJ
Thorneloe
Kevin S
KS
D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003556:Cystitis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D062558:NAV1.9 Voltage-Gated Sodium Channel; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000172:deficiency / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000172:deficiency / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects / Q000235:genetics*
D018501:Antirheumatic Agents; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C491885:Scn11a protein, mouse; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D003520:Cyclophosphamide; D015232:Dinoprostone; D019342:Acetic Acid