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1 Department of Endocrinology and Reproduction Research Branch, NIH, NICHD, Bethesda, MD, USA
* To whom correspondence should be addressed. E-mail: stankos{at}helix.nih.gov.
Extracellular nucleotide-activated purinergic receptors (P2XRs) are a family of cation-permeable channels that conduct small cations, including Ca2+, leading to the depolarization of cells and subsequent stimulation of voltage-gated Ca2+ influx in excitable cells. Here we studied the spatio-temporal characteristics of intracellular Ca2+ signaling and its dependence on current signaling in excitable GT1 and non-excitable HEK293 cells expressing wild type and chimeric P2XRs. In both cell types, P2XR generated depolarizing currents during the sustained ATP stimulation, which desensitized in order (from rapidly desensitizing to non-desensitizing): P2X3R > P2X2b+X4R > P2X2bR > P2X2a+X4R > P2X4R > P2X2aR > P2X7R. HEK293 cells were not suitable for studies on P2XR-mediated Ca2+ influx because of the co-activation of endogenously expressed Ca2+-mobilizing purinergic P2Y receptors. However, when expressed in GT1 cells all wild type and chimeric P2XRs responded to agonist binding with global Ca2+ signals, which desensitized in the same order as current signals but in a significantly slower manner. The global distribution of Ca2+ signals was present independently of the rate of current-desensitization. The temporal characteristics of Ca2+ signals were not affected by voltage-gated calcium influx and removal of extracellular sodium. Calcium signals reflected well the receptor-specific EC50s for ATP and the extracellular zinc and pH sensitivities of P2XRs. These results indicate that intracellular Ca2+ measurements are useful for characterizing the pharmacological properties and messenger functions of P2XRs, as well as the kinetics of channel activity, when the host cells do not express other members of purinergic receptors.
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