QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 6, 2006, 26(36):9340-9348; doi:10.1523/JNEUROSCI.2635-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal 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 Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Filippov, A. K. Articles by Brown, D. A. Search for Related Content PubMed PubMed Citation Articles by Filippov, A. K. Articles by Brown, D. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB POTASSIUM

 Previous Article

Cellular/Molecular
Activation of P2Y₁ Nucleotide Receptors Induces Inhibition of the M-Type K⁺ Current in Rat Hippocampal Pyramidal Neurons

Alexander K. Filippov,¹ Roy C. Y. Choi,² Joseph Simon,² Eric A. Barnard,² and David A. Brown¹

¹Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom, and ²Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom

Correspondence should be addressed to Dr. Alexander K. Filippov, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.filippov{at}ucl.ac.uk

We have shown previously that stimulation of heterologously expressed P2Y₁ nucleotide receptors inhibits M-type K⁺ currents in sympathetic neurons. We now report that activation of endogenous P2Y₁ receptors induces inhibition of the M-current in rat CA1/CA3 hippocampal pyramidal cells in primary neuron cultures. The P2Y₁ agonist adenosine 5'-[-thio]diphosphate trilithium salt (ADPS) inhibited M-current by up to 52% with an IC₅₀ of 84 nM. The hydrolyzable agonist ADP (10 µM) produced 32% inhibition, whereas the metabotropic glutamate receptor 1/5 agonist DHPG [(S)-3,5-dihydroxyphenylglycine] (10 µM) inhibited M-current by 44%. The M-channel blocker XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride] produced 73% inhibition at 3 µM; neither ADPS nor ADP produced additional inhibition in the presence of XE991. The effect of ADPS was prevented by a specific P2Y₁ antagonist, MRS 2179 (2'-deoxy-N'-methyladenosine-3',5'-bisphosphate tetra-ammonium salt) (30 µM). Inhibition of the M-current by ADPS was accompanied by increased neuronal firing in response to injected current pulses. The neurons responding to ADPS were judged to be pyramidal cells on the basis of (1) morphology, (2) firing characteristics, and (3) their distinctive staining for the pyramidal cell marker neurogranin. Strong immunostaining for P2Y₁ receptors was shown in most cells in these cultures: 74% of the cells were positive for both P2Y₁ and neurogranin, whereas 16% were only P2Y₁ positive. These results show the presence of functional M-current-inhibitory P2Y₁ receptors on hippocampal pyramidal neurons, as predicted from their effects when expressed in sympathetic neurons. However, the mechanism of inhibition in the two cell types seems to differ because, unlike nucleotide-mediated M-current inhibition in sympathetic neurons, that in hippocampal neurons did not appear to result from raised intracellular calcium

Key words: nucleotide receptors; P2Y receptors; hippocampus; pyramidal neurons; potassium channels; M-current

---

Received March 14, 2006; revised July 31, 2006; accepted Aug. 3, 2006.

Correspondence should be addressed to Dr. Alexander K. Filippov, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: a.filippov{at}ucl.ac.uk

This article has been cited by other articles:

				G. Li and J. E. Olson Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1550 - C1560. [Abstract] [Full Text] [PDF]

				R. C. Y. Choi, J. Simon, K. W. K. Tsim, and E. A. Barnard Constitutive and Agonist-induced Dimerizations of the P2Y1 Receptor: RELATIONSHIP TO INTERNALIZATION AND SCAFFOLDING J. Biol. Chem., April 18, 2008; 283(16): 11050 - 11063. [Abstract] [Full Text] [PDF]

				O. Zaika, G. P. Tolstykh, D. B. Jaffe, and M. S. Shapiro Inositol Triphosphate-Mediated Ca2+ Signals Direct Purinergic P2Y Receptor Regulation of Neuronal Ion Channels J. Neurosci., August 15, 2007; 27(33): 8914 - 8926. [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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help