[Effects of modulators of calcium metabolism on mesenteric artery contractions during activation of P2X receptors in guinea-pig].

ATP evokes changes in the vascular tone through the activation of P2X and P2Y purinoceptors. To evaluate relative contribution of Ca2+ entry through the L-type voltage-gated calcium channels and Ca2+ -induced Ca2+ -release (CICR) mechanisms in initiation of vascular smooth muscle contraction induced by P2XRs activation, we have applied P2X receptor agonist -meATP (10 microM) and measured changes in phasic isometric tension of endothelium-denuded mesenteric artery rings in the presence of antagonists IP3Rs (60 mcmol/l APB) or RyRs (100 mcmol/l tetracaine) combined with on-off modulation of the L-type calcium channels by nicardipine (5 microM). We found that activation of P2XRs results in Ca2+ release from SR through both IP3Rs and RyRs. In addition, Ca2+ entry via L-type Ca2+ channels also participates in Ca2+ release from SR presumably through CICR mechanism. However, the phasic contractions in the presence of nicardipine were found to be less sensitive to inhibition of IP3Rs than RyRs (47.1 +/- 9.5% and 22.9 +/- 1.4% comparing to 38.3 +/- 9.6% and 518 +/- 7.8% in control solution for IP3R and RyR inhibition, respectively). This finding suggests that Ca2+ entered the cell through L-type Ca2+ channels, has easier access to IP3Rs than to RyRs. This suggestion is further supported by immunostaining IP3Rs and RyRs. Confocal imaging revealed that sub-PM SR elements are enriched with IP3Rs, while RyRs are predominantly located in the central/perinuclear SR elements.