Abstract
ATP-gated purinergic receptors (P2XRs) are a family of cation-permeable channels that conduct Ca2+ and facilitate voltage-sensitive Ca2+ entry in excitable cells. To study Ca2+signaling by P2XRs and its dependence on voltage-sensitive Ca2+ influx, we expressed eight cloned P2XR subtypes individually in gonadotropin-releasing hormone-secreting neurons. In all cases, ATP evoked an inward current and a rise in [Ca2+]i. P2XR subtypes differed in the peak amplitude of [Ca2+]i response independently of the level of receptor expression, with the following order: P2X1R < P2X3R < P2X4R < P2X2bR < P2X2aR < P2X7R. During prolonged agonist stimulation, Ca2+ signals desensitized with different rates: P2X3R > P2X1R > P2X2bR > P2X4R ≫ P2X2aR ≫ P2X7R. The pattern of [Ca2+]iresponse for each P2XR subtype was highly comparable with that of the depolarizing current, but the activation and desensitization rates were faster for the current than for [Ca2+]i. The P2X1R, P2X3R, and P2X4R-derived [Ca2+]i signals were predominantly dependent on activation of voltage-sensitive Ca2+ influx, both voltage-sensitive and -insensitive Ca2+ entry pathways equally contributed to [Ca2+]i responses in P2X2aR- and P2X2bR-expressing cells, and P2X7R operated as a nonselective pore capable of conducting larger amounts of Ca2+ independently on the status of voltage-gated Ca2+ channels. Thus, Ca2+signaling by homomeric P2XRs expressed in an excitable cell is subtype-specific, which provides an effective mechanism for generating variable [Ca2+]i patterns in response to a common agonist.
Footnotes
- Received February 4, 2000.
- Accepted July 17, 2000.
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Send reprint requests to: Dr. Stanko Stojilkovic, Section on Cellular Signaling, ERRB/NICHD/NIH, Bldg. 49, Room 6A-36, 49 Convent Drive, Bethesda, MD 20892. E-mail:stankos{at}helix.nih.gov
- The American Society for Pharmacology and Experimental Therapeutics
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