Nicotinic receptor activation on primary sensory afferents modulates autorhythmicity in the mouse renal pelvis

Michael J Nguyen, S Angkawaijawa, Hikaru Hashitani, Richard J Lang

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6 Citations (Scopus)


BACKGROUND AND PURPOSE: The modulation of the spontaneous electrical and Ca2+ signals underlying pyeloureteric peristalsis upon nicotinic receptor activation located on primary sensory afferents (PSAs) was investigated in the mouse renal pelvis. EXPERIMENTAL APPROACH: Contractile activity was followed using video microscopy, electrical and Ca2+ signals in typical and atypical smooth muscle cells (TSMCs and ASMCs) within the renal pelvis were recorded separately using intracellular microelectrodes and Fluo-4 Ca2+ imaging. KEY RESULTS: Nicotine and carbachol (1-100 muM) transiently reduced the frequency and increased the amplitude of spontaneous phasic contractions in a manner unaffected by muscarininc antagonists, 4-DAMP and pirenzipine (10 nM) or L-NAME (200 muM), inhibitor of nitric oxide synthesis, but blocked by the nicotinic antagonist, hexamethonium or capsaicin, depletor of PSA neuropeptides. These negative chronotropic and delayed positive inotropic effects of carbachol on TSMC contractions, action potentials and Ca2+ transients were inhibited by glibenclamide (1 muM), blocker of ATP dependent K channels (KATP). Nicotinic receptor-evoked inhibition of the spontaneous Ca2+ transients in ASMCs was prevented by capsaicin but not glibenclamide. In contrast, the negative inotropic and chronotropic effects of the non-selective cyclooxygenase inhibitor indomethacin were not prevented by glibenclamide. CONCLUSIONS IMPLICATIONS: The negative chronotropic effect of nicotinic receptor activation results from the release of CGRP from PSAs which suppresses Ca2+ signalling in ASMCs. PSA-released CGRP also evokes a transient hyperpolarization in TSMCs upon the opening of KATP channels, which reduces contraction propagation but promotes the recruitment of TSMC Ca2+ channels that underlie the delayed positive inotropic effects of carbachol.
Original languageEnglish
Pages (from-to)1221 - 1232
Number of pages12
JournalBritish Journal of Pharmacology
Issue number6
Publication statusPublished - 2013

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