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Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium
Author(s) -
Zagorodnyuk Vladimir P.,
Brookes Simon J. H.,
Spencer Nick J.,
Gregory Sarah
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.172577
Subject(s) - chemistry , capsazepine , capsaicin , mechanotransduction , antagonist , free nerve ending , endocrinology , biophysics , medicine , neuroscience , trpv1 , transient receptor potential channel , biology , biochemistry , receptor
The guinea pig bladder is innervated by at least five distinct major classes of extrinsic sensory neurons. In this study, we have examined the mechanisms of mechanotransduction and chemosensitivity of two classes of bladder afferents that have their endings in the vicinity of the urothelium: stretch‐sensitive muscle‐mucosal mechanoreceptors and stretch‐insensitive, mucosal high‐responding afferents. The non‐selective P2 purinoreceptor antagonist pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid did not affect stretch‐ or stroking‐induced firing of these afferents but significantly reduced the excitatory action of α,β‐methylene ATP. Blocking synaptic transmission in Ca 2+ ‐free solution did not affect stretch‐evoked firing but slightly reduced stretch‐induced tension responses. Stroking‐induced firing of both classes of afferents was also not affected in Ca 2+ ‐free solution. Of blockers of mechano‐gated channels, benzamil (100 μ m ), but not amiloride (100 μ m ), Gd 3+ (100 μ m ) or SKF 96365 (50 μ m ), inhibited stretch‐ and stroking‐induced firing. Serotonin (100 μ m ) applied directly onto receptive fields predominantly activated muscle‐mucosal afferents. Muscarine (100 μ m ) and substance P (100 μ m ) in 24% and 36% cases activated only mucosal high‐responding units. Bradykinin (10 μ m ), but not prostaglandin E2 (10 μ m ), excites predominantly mucosal units. High (80 m m ) K + solution activated both afferent classes, but responses of mucosal units were 4 times greater. In contrast to muscle‐mucosal units, most mucosal high‐responding units were activated by hot Krebs solution (45–46°C), low pH (pH 4) and capsaicin (3 μ m ). TRPV1 antagonist, capsazepine (10 μ m ) was without effect on mechanotransduction by mucosal high‐responding afferents. The results show that mechanotransduction of these two types of afferents are not dependant upon Ca 2+ ‐dependent exocytotic release of mediators, or ATP, and it is likely that benzamil‐sensitive stretch‐activated ion channels on their endings are involved in direct mechanotransduction. The chemosensitivity to agonists and noxious stimuli differs significantly between these two major classes of bladder afferents that reflects their different physiological and pathophysiological roles in the bladder.