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

This Article Full Text Full Text (PDF) All Versions of this Article: mol.106.026625v1 70/5/1494    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services 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 Google Scholar Google Scholar Articles by Shah, M. M. Articles by Haylett, D. G. Search for Related Content PubMed PubMed Citation Articles by Shah, M. M. Articles by Haylett, D. G.

Enhancement of Hippocampal Pyramidal Cell Excitability by the Novel Selective Slow-Afterhyperpolarization Channel Blocker 3-(Triphenylmethylaminomethyl)pyridine (UCL2077)

Departments of Pharmacology (M.M.S., D.C.H.B., D.G.H.) and Chemistry (M.J.-T., C.R.G.), University College London, Gower Street, London, United Kingdom

The slow afterhyperpolarization (sAHP) in hippocampal neurons has been implicated in learning and memory. However, its precise role in cell excitability and central nervous system function has not been explicitly tested for 2 reasons: 1) there are, at present, no selective inhibitors that effectively reduce the underlying current in vivo or in intact in vitro tissue preparations, and 2) although it is known that a small conductance K⁺ channel that activates after a rise in [Ca²⁺]_i underlies the sAHP, the exact molecular identity remains unknown. We show that 3-(triphenylmethylaminomethyl)pyridine (UCL2077), a novel compound, suppressed the sAHP present in hippocampal neurons in culture (IC₅₀ = 0.5 µM) and in the slice preparation (IC₅₀ 10 µM). UCL2077 was selective, having minimal effects on Ca²⁺ channels, action potentials, input resistance and the medium afterhyperpolarization. UCL2077 also had little effect on heterologously expressed small conductance Ca²⁺-activated K⁺ (SK) channels. Moreover, UCL2077 and apamin, a selective SK channel blocker, affected spike firing in hippocampal neurons in different ways. These results provide further evidence that SK channels are unlikely to underlie the sAHP. This study also demonstrates that UCL2077, the most potent, selective sAHP blocker described so far, is a useful pharmacological tool for exploring the role of sAHP channels in the regulation of cell excitability in intact tissue preparations and, potentially, in vivo.

Address correspondence to: Mala M. Shah, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT UK. E-mail: mala.shah{at}ucl.ac.uk

This article has been cited by other articles:

				L. Zhang, L. P. Renaud, and M. Kolaj Properties of a T-Type Ca2+Channel-Activated Slow Afterhyperpolarization in Thalamic Paraventricular Nucleus and Other Thalamic Midline Neurons J Neurophysiol, June 1, 2009; 101(6): 2741 - 2750. [Abstract] [Full Text] [PDF]

				N. Gu, H. Hu, K. Vervaeke, and J. F. Storm SK (KCa2) Channels Do Not Control Somatic Excitability in CA1 Pyramidal Neurons But Can Be Activated by Dendritic Excitatory Synapses and Regulate Their Impact J Neurophysiol, November 1, 2008; 100(5): 2589 - 2604. [Abstract] [Full Text] [PDF]