HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 94/3/2195    most recent 00035.2005v2 00035.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Wollmann, G. Articles by van den Pol, A. N. Search for Related Content PubMed PubMed Citation Articles by Wollmann, G. Articles by van den Pol, A. N.

Direct Excitation of Hypocretin/Orexin Cells by Extracellular ATP at P2X Receptors

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut

Submitted 10 January 2005; accepted in final form 8 June 2005

Hypocretin/orexin (hcrt) neurons play an important role in hypothalamic arousal and energy homeostasis. ATP may be released by neurons or glia or by pathological conditions. Here we studied the effect of extracellular ATP on hypocretin cells using whole cell patch-clamp recording in hypothalamic slices of transgenic mice expressing green fluorescent protein (GFP) exclusively in hcrt-producing cells. Local application of ATP induced a dose-dependent increase in spike frequency. In the presence of TTX, ATP (100 µM) depolarized the cells by 7.8 ± 1.2 mV. In voltage clamp under blockade of synaptic activity with the GABA_A receptor antagonist bicuculline, and ionotropic glutamate receptor antagonists DL-2-amino-5-phosphonopentanoic acid (AP-5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), ATP (100 µM) evoked an 18 pA inward current. The inward current was blocked by extracellular choline substitution for Na⁺, had a reversal potential of –27 mV, and was not affected by nominally Ca²⁺-free external buffer, suggesting that ATP activated a nonselective cation current. All excitatory effects of ATP showed rapid attenuation. ATP-induced excitatory actions were mimicked by nonhydrolyzable ATP--S but not by ,-MeATP and inhibited by the purinoceptor antagonists suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS). The current was potentiated by a decrease in bath pH, suggesting P2X₂ subunit involvement. Frequency and amplitude of spontaneous and miniature synaptic events were not altered by ATP. Suramin, but not PPADS, caused a small suppression of evoked excitatory synaptic potentials. Together, these results show a depolarizing response to extracellular ATP that would lead to an increased activity of the hypocretin arousal system.

This article has been cited by other articles:

				J. Hara, D. Gerashchenko, J. P. Wisor, T. Sakurai, X. Xie, and T. S. Kilduff Thyrotropin-Releasing Hormone Increases Behavioral Arousal through Modulation of Hypocretin/Orexin Neurons J. Neurosci., March 25, 2009; 29(12): 3705 - 3714. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				A. N. van den Pol, M. D. Robek, P. K. Ghosh, K. Ozduman, P. Bandi, M. D. Whim, and G. Wollmann Cytomegalovirus InducesInterferon-Stimulated Gene Expression and Is Attenuated by Interferon in the Developing Brain J. Virol., January 1, 2007; 81(1): 332 - 348. [Abstract] [Full Text] [PDF]