RT Journal Article
SR Electronic
T1 Characterization of Calcium Signaling by Purinergic Receptor-Channels Expressed in Excitable Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 936
OP 945
DO 10.1124/mol.58.5.936
VO 58
IS 5
A1 Taka-aki Koshimizu
A1 Fredrick Van Goor
A1 Melanija Tomić
A1 Anderson On-Lam Wong
A1 Akito Tanoue
A1 Gozoh Tsujimoto
A1 Stanko S. Stojilkovic
YR 2000
UL http://molpharm.aspetjournals.org/content/58/5/936.abstract
AB 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.