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

• Published in: Pharmacological reports 2013-01, Vol.65 (1), p.152-163
• Main Authors: Sukhanova, Khrystyna Yu, Harhun, Maksym I., Bouryi, Vitali A., Gordienko, Dmitri V.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - administration & dosage; Adenosine Triphosphate - analogs & derivatives; Animals; Ca2+ signaling; Ca2+-induced Ca2+ release; Calcium - metabolism; Calcium Channels, L-Type - metabolism; Calcium Signaling; confocal microscopy; Drug Safety and Pharmacovigilance; Guinea Pigs; Male; Mesenteric Arteries - metabolism; Microscopy, Confocal; Myocytes, Smooth Muscle - metabolism; P2X receptors; Pharmacotherapy; Pharmacy; Receptors, Purinergic P2X - metabolism; vascular smooth muscle cells; voltage-gated calcium channels
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(13)70973-3

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. 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 ab-meATP-induced [Ca2+]i transients were analyzed. 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. 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.