title: Nicotinic receptor activation on primary sensory afferents modulates autorhythmicity in the mouse renal pelvis.
abstract: OBJECTIVE
  The modulation of the spontaneous electrical and Ca(2+) signals underlying pyeloureteric peristalsis upon nicotinic receptor activation located on primary sensory afferents (PSAs) was investigated in the mouse renal pelvis.
  
  
  METHODS
  Contractile activity was followed using video microscopy, electrical and Ca(2+) signals in typical and atypical smooth muscle cells (TSMCs and ASMCs) within the renal pelvis were recorded separately using intracellular microelectrodes and Fluo-4 Ca(2+) imaging.
  
  
  RESULTS
  Nicotine and carbachol (CCh; 1-100 μM) transiently reduced the frequency and increased the amplitude of spontaneous phasic contractions in a manner unaffected by muscarininc antagonists, 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide) and pirenzipine (10 nM) or L-NAME (L-Nω-nitroarginine methyl ester; 200 μM), inhibitor of NO synthesis, but blocked by the nicotinic antagonist, hexamethonium or capsaicin, depletor of PSA neuropeptides. These negative chronotropic and delayed positive inotropic effects of CCh on TSMC contractions, action potentials and Ca(2+) transients were inhibited by glibenclamide (Glib; 1 μM), blocker of ATP-dependent K (KATP) channels. Nicotinic receptor-evoked inhibition of the spontaneous Ca(2+) transients in ASMCs was prevented by capsaicin but not Glib. In contrast, the negative inotropic and chronotropic effects of the non-selective COX inhibitor indomethacin were not prevented by Glib.
  
  
  CONCLUSIONS
  The negative chronotropic effect of nicotinic receptor activation results from the release of calcitonin gene-related peptide (CGRP) from PSAs, which suppresses Ca(2+) 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 Ca(2+) channels that underlie the delayed positive inotropic effects of CCh.
authors.affiliation: Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Vic., Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Angkawaijawa
authors.forename: H
authors.initials: H
authors.lastname: Hashitani
authors.forename: R J
authors.initials: RJ
authors.lastname: Lang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D005260:Female; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D007682:Kidney Pelvis / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology
chemical_list: D054086:KATP Channels; D018733:Nicotinic Antagonists; D026902:Potassium Channel Blockers; D011978:Receptors, Nicotinic; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium
keywords: nicotinic receptors primary sensory afferents; pyeloureteric peristalsis; smooth muscle; upper urinary tract