Nucleotide-Induced Ca2+ Signaling in Sustentacular Supporting Cells of the Olfactory Epithelium

Extracellular purines and pyrimidines are important Signaling molecules acting via purinergic cell-surface receptors in neurons, glia, and glia-like cells such as sustentacular supporting cells (SCs) of the olfactory epithelium (OE). Here, we thoroughly characterize ATP-induced responses in SCs of the OE using functional Ca2+ image The initial ATP-induced increase of the intracellular Ca2+ concentration [Ca2+](i) always occurred in the apical part of SCs and subsequently propagated toward the basal lamina, indicating the occurrence of purinergic receptors I the apical part of SCs. The mean propagation velocity of the Ca2+ signal within SCs was 17.10 +/- 1.02 mu m/s. ATP evoked increases in [Ca2+](i) in both the presence and absence of extracellular Ca2+. Depletion of the intracellular Ca2+ stores abolished the responses. This shows that the ATP-induced [Ca2+](i) increases were in large part, if not entirely, due to the activation of G protein-coupled receptors followed by Ca2+ mobilization from intracellular stores, suggesting an involvement of P2Y receptors. The order of potency of the applied purinergic agonists was UTP > ATP > ATP-gamma S (with all others being only weakly active or inactive). The ATP-induced [Ca2+](i) increases could be reduced by the purinergic antagonists PPADS and RB2, but not by suramin. Our findings suggest that extracellular nucleotides in the OE activate SCs via P2Y(2)/P2Y(4)-like receptors and initiate a characteristic intraepithelial Ca2+ wave. (C) 2008 Wiley-Liss, Inc.