Mechanisms of [Ca2+]i elevation following P2X receptor activation in the guinea-pig small mesenteric artery myocytes

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 [ca 2+]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 ca 2+-induced ca2+ release significantly more than ca 2+ 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 ca 2+ permeable,per se form less effective ca2+ signaling pathway. this study,therefore,rescales potential targets for therapeutic intervention in purinergic control of vascular tone. copyright © 2013 by institute of pharmacology polish academy of sciences.