title: Distinct effects of CGRP on typical and atypical  smooth muscle cells involved in generating  spontaneous contractions in the mouse renal pelvis.
abstract: OBJECTIVE
  We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene-related peptide (CGRP).
  
  
  METHODS
  Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo-4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out.
  
  
  RESULTS
  Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1-positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve-mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5-hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP-sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs.
  
  
  CONCLUSIONS
  The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP-sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L-type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients.
authors.affiliation: Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hasitani@med.nagoya-cu.ac.jp
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lang
authors.forename: Retsu
authors.initials: R
authors.lastname: Mitsui
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Mabuchi
authors.forename: Hikaru
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D054086:KATP Channels / Q000378:metabolism; D007682:Kidney Pelvis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008839:Microelectrodes; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D054086:KATP Channels; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium