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Modulation of heteromeric P2X1/5 receptors by phosphoinositides in astrocytes depends on the P2X1 subunit

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Ase, Ariel R., Bernier, Louis-Philippe, Blais, Dominique, Pankratov, Yuriy and Seguela, Philippe. (2010) Modulation of heteromeric P2X1/5 receptors by phosphoinositides in astrocytes depends on the P2X1 subunit. Journal of Neurochemistry, Vol.113 (No.6). pp. 1676-1684. ISSN 0022-3042

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Official URL: http://dx.doi.org/10.1111/j.1471-4159.2010.06734.x

Abstract

Purinergic signaling is critical for neuron-glia communication. Glial cells participate in synaptic transmission and express metabotropic P2Y as well as ionotropic P2X ATP receptors. In astrocytes, endogenous ATP-evoked currents with kinetics and pharmacology characteristic of the heteromeric P2X1/5 receptor channel have recently been reported. We investigated the interaction of major phosphoinositides with heteromeric P2X1/5 channels. Using patch-clamp electrophysiology on enhanced green fluorescent protein-expressing astrocytes acutely isolated from cortical slices of transgenic mice, we report a strong modulation of P2X1/5-like currents by phosphoinositides. Wortmannin-induced depletion of phosphoinositides decreases the amplitude of both the fast and sustained component of the P2X1/5-like currents although recovery and kinetics remain intact. In transfected human embryonic kidney cells, we provide evidence that depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] levels significantly decreases P2X1/5 currents while intracellular application of PI(4,5)P-2 completely rescued P2X1/5 currents, ruling out the involvement of phosphatidylinositol 3,4,5-trisphosphate. In contrast to P2X1, homomeric P2X5 current responses were found insensitive to phosphoinositides, and the C-terminus of P2X5 subunit lacked binding to phospholipids in an overlay assay. Our results suggest that the contribution of calcium-permeable heteromeric P2X1/5 receptor channels to the excitability of astrocytes is modulated by PI(4,5)P-2 through the P2X1 lipid-binding domain.

Item Type:

Journal Article

Subjects:

Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Divisions:

Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)

Journal or Publication Title:

Journal of Neurochemistry

Publisher:

Wiley-Blackwell Publishing Ltd.

ISSN:

0022-3042