Nucleotide‐induced Ca 2+ signaling in sustentacular supporting cells of the olfactory epithelium

Abstract 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 Ca 2+ imaging. The initial ATP‐induced increase of the intracellular Ca 2+ concentration [Ca 2+ ] i always occurred in the apical part of SCs and subsequently propagated toward the basal lamina, indicating the occurrence of purinergic receptors in the apical part of SCs. The mean propagation velocity of the Ca 2+ signal within SCs was 17.10 ± 1.02 μm/s. ATP evoked increases in [Ca 2+ ] i in both the presence and absence of extracellular Ca 2+ . Depletion of the intracellular Ca 2+ stores abolished the responses. This shows that the ATP‐induced [Ca 2+ ] i increases were in large part, if not entirely, due to the activation of G protein‐coupled receptors followed by Ca 2+ mobilization from intracellular stores, suggesting an involvement of P2Y receptors. The order of potency of the applied purinergic agonists was UTP > ATP > ATPγS (with all others being only weakly active or inactive). The ATP‐induced [Ca 2+ ] 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 Ca 2+ wave. © 2008 Wiley‐Liss, Inc.