Research Topics
Purinergic signaling in the olfactory epithelium
Supporting cells
Supporting cells (green), ORNs (red).
Sustentacular supporting cells (SCs) of the OE of larval Xenopus laevis are sensitive to extracellular application of ATP.
Intracellular Ca2+ wave in a single supporting cell.
A detailed investigation of these nucleotide-induced responses showed that extracellular nucleotides in the OE activate SCs via P2Y2/P2Y4-like receptors and initiate a characteristic intraepithelial Ca2+ wave propagating from the apical part of SCs towards the basal lamina of the OE (Hassenklöver et al., 2008).
It will be critical for our understanding of the OE to determine the physiological role of this intraepithelial signaling, to determine possible physiological sources of extracellular ATP and to investigate a possible involvement of the spatiotemporal pattern of [Ca2+]i increases in SCs in triggering a crosstalk between different cell types of the OE.
Basal cells
Ca2+ signaling in basal stem cells (bottom left) upon ATP application.
We recently discovered that nucleotides also evoke Ca2+-signals in basal stem/progenitor cells of the OE (Hassenklöver et al., 2009). These Ca2+-signals are mediated by P2Y receptors, which show a differing pharmacological profile to those expressed by supporting cells. Blocking purinergic receptors significantly reduced the number of proliferating cells in the basal cell layer (for more information see Regeneration & differentiation). This implicates that nucleotides are modulating the proliferating activity of basal stem/progenitor cells of the OE. A connection between the purinergic signaling pathways in supporting and basal cells, for example via active nucleotide release, seems to be likely.
Purinergic signaling in the anterior telencephalon
The anterior telencephalon consists of the olfactory bulb (OB), the first relay station for olfactory information, and the periventricular zone (PVZ) of the lateral ventricles (lv). The PVZ gives rise to new neurons, which integrate into the OB circuitry throughout the lifetime of an organism.
The anterior telencephalon contains the proliferative PVZ.
Cells of the OB and the PVZ of larval Xenopus laevis are sensitive to extracellular nucleotides. Both regions show differences in the expression of purinergic receptor subtypes. A pharmacological investigation led to the conclusion that OB cells express almost exclusively ionotropic P2X receptors, whereas PVZ cells express predominantly P2X, but also metabotropic P1 and P2Y receptors (Hassenklöver et al., 2010).
Nucleotides evoke Ca2+ signals in the anterior telencephalon.
Constant application of potent P2 agonists and antagonists does not alter the neuronal calcium signals in the OB evoked by odorant stimulation. Hence, the physiological function of the telencephalic purinergic system is still unclear, but a modulatory role in the processing of olfactory information seems unlikely (Hassenklöver et al., 2010). A possible involvement in the generation of new neurons in the PVZ or the sorting of bulbar interneurons via apotosis needs to be investigated.