Tetrodotoxin-sensitive voltage-gated sodium channels regulate bladder afferent responses to distension

Pain
Luke GrundyStuart M Brierley

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent, chronic bladder disorder that negatively impacts the quality of life for ∼5% of the western population. Hypersensitivity of mechanosensory afferents embedded within the bladder wall is considered a key component in mediating IC/BPS symptoms. Bladder infusion of voltage-gated sodium (Nav) channel blockers show clinical efficacy in treating IC/BPS symptoms; however, the current repertoire of Nav channels expressed by and contributing to bladder afferent function is unknown. We used single-cell reverse-transcription polymerase chain reaction of retrogradely traced bladder-innervating dorsal root ganglia (DRG) neurons to determine the expression profile of Nav channels, and patch-clamp recordings to characterise the contribution of tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Nav channels to total sodium current and neuronal excitability. We determined the TTX-S and TTX-R contribution to mechanosensitive bladder afferent responses ex vivo and spinal dorsal horn activation in vivo. Single-cell reverse-transcription polymerase chain reaction of bladder-innervating DRG neurons revealed significant heterogeneity in Nav channel coexpression pattern...Continue Reading

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Citations

Dec 4, 2019·American Journal of Physiology. Renal Physiology·Luke GrundyStuart M Brierley
Sep 29, 2018·Marine Drugs·Daria I MelnikovaTimur Yu Magarlamov
Jan 9, 2019·Frontiers in Neuroscience·Luke GrundyStuart M Brierley
Aug 7, 2021·Toxins·Ana Campos-RíosJosé Antonio Lamas
Nov 6, 2021·Journal of Neural Engineering·Calvin D EiberJames B Fallon

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