P2X(7) RECEPTOR ACTIVATION-INDUCED CONTRACTION AND LYSIS IN HUMAN SAPHENOUS-VEIN SMOOTH-MUSCLE

In cutaneous veins where purinergic neurotransmission is more prominen t compared with in deep vessels, physiological and pathological roles of nerve-released ATP have been described. Neuronally released ATP has been reported to act through activation of unidentified ionotropic P2 X receptor(s), This study analyzed P2X receptor subtypes expressed in human saphenous vein smooth muscle and their physiological functions. Transcripts for both hP2X(1) receptors, already identified in other sm ooth muscles, and, surprisingly, kP2X(7) receptors known to be respons ible for the cytotoxic effect of ATP in macrophages were detected by N orthern blot analysis in total RNA from saphenous vein smooth muscle. ATP and other P2X receptor agonists [alpha beta-methylene-ATP, 2-methy lthio-ATP, and 2',3'-(4-benzoyl)benzoyl-ATP] dose-dependently contract ed venous rings, but the contraction induced by 2-methylthio-ATP was m ore transient than that evoked by the other P2X agonists, The effect o f hP2X(1) agonists involved the activation of a rapidly desensitizing cation current recorded in freshly isolated myocytes. The action of kP 2X(7) receptor agonists was related to a maintained nondesensitizing c ation current. in addition, hP2X(7) receptor activation formed membran e pores that were permeable to large molecules. hP2X(1) and hP2X(7) re ceptors coexpressed in COS cells did not associate to form heteromulti mers. Our data indicate that both hP2X(1) and hP2X(7) receptors are ex pressed as 2 separated populations of channels in human saphenous vein myocytes and are involved in ATP-induced tension. We suggest that cel l lysis consequent to hP2X(7) receptor-induced pore formation contribu tes to the disorganization and decrease in the amount of contractile m yocytes in the media of varicose veins.