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Vol. 58, Issue 5, 936-945, November 2000
,
Endocrinology and Reproduction Research Branch, National Institute
of Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland (T.K., F.V.G., M.T., A.O.-L.W., S.S.S.); and
Department of Molecular Cellular Pharmacology, National Children's
Medical Research Center, Tokyo, Japan (A.K., G.T.)
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+]i
response 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.
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