title: Mechanisms of [Ca2+]i elevation following P2X receptor activation in the guinea-pig small mesenteric artery myocytes.
abstract: BACKGROUND
  There is growing evidence suggesting involvement of L-type voltage-gated Ca2+ channels (VGCCs) in purinergic signaling mechanisms. However, detailed interplay between VGCCs and P2X receptors in intracellular Ca2+ mobilization is not well understood. This study examined relative contribution of the Ca2+ entry mechanisms and induced by this entry Ca2+ release from the intracellular stores engaged by activation of P2X receptors in smooth muscle cells (SMCs) from the guinea-pig small mesenteric arteries.
  
  
  METHODS
  P2X receptors were stimulated by the brief local application of αβ-meATP and changes in [Ca2+]i were monitored in fluo-3 loaded SMCs using fast x-y confocal Ca2+ imaging. The effects of the block of L-type VGCCs and/or depletion of the intracellular Ca2+ stores on αβ-meATP-induced [Ca2+]i transients were analyzed.
  
  
  RESULTS
  Our analysis revealed that Ca2+ entry via L-type VGCCs is augmented by the Ca2+-induced Ca2+ release significantly more than Ca2+ entry via P2X receptors, even though net Ca2+ influxes provided by the two mechanisms are not significantly different.
  
  
  CONCLUSIONS
  Thus, arterial SMCs upon P2X receptor activation employ an effective mechanism of the Ca2+ signal amplification, the major component of which is the Ca2+ release from the SR activated by Ca2+ influx via L-type VGCCs. This signaling pathway is engaged by depolarization of the myocyte membrane resulting from activation of P2X receptors, which, being Ca2+ permeable, per se form less effective Ca2+ signaling pathway. This study, therefore, rescales potential targets for therapeutic intervention in purinergic control of vascular tone.
authors.affiliation: Laboratory of Molecular Pharmacology and Biophysics of Cell Signalling, A.A. Bogomoletz, Institute of Physiology, Bogomoletz 4, Kiev, 01024, Ukraine. skhrist@biph.kiev.ua
authors.forename: Khrystyna Yu
authors.initials: KY
authors.lastname: Sukhanova
authors.forename: Maksym I
authors.initials: MI
authors.lastname: Harhun
authors.forename: Vitali A
authors.initials: VA
authors.lastname: Bouryi
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Gordienko
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D006168:Guinea Pigs; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058469:Receptors, Purinergic P2X / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium