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J. Neurosci. 29 (8): 2371-2383

Copyright © 2009 by the Society for Neuroscience.

Cellular/Molecular

Membrane Lipid Modulations Remove Divalent Open Channel Block from TRP-Like and NMDA Channels

Moshe Parnas,1 Ben Katz,1 Shaya Lev,1 Vered Tzarfaty,1 Daniela Dadon,1 Ariela Gordon-Shaag,1,3 Henry Metzner,2 Rami Yaka,2 , and Baruch Minke1

1Department of Physiology and the Kühne Minerva Center for Studies of Visual Transduction, 2Department of Pharmacology, Faculty of Medicine of The Hebrew University, and 3Hadassah Academic College, Jerusalem 91120, Israel

Correspondence should be addressed to Baruch Minke, Department of Physiology, Faculty of Medicine, The Hebrew University, P. O. Box 12272, Jerusalem 91120, Israel. Email: minke{at}md.huji.ac.il

Abstract: Open channel block is a process in which ions bound to the inside of a channel pore block the flow of ions through that channel. Repulsion of the blocking ions by depolarization is a known mechanism of open channel block removal. For the NMDA channel, this mechanism is necessary for channel activation and is involved in neuronal plasticity. Several types of transient receptor potential (TRP) channels, including the Drosophila TRP and TRP-like (TRPL) channels, also exhibit open channel block. Therefore, removal of open channel block is necessary for the production of the physiological response to light. Because there is no membrane depolarization before the light response develops, it is not clear how the open channel block is removed, an essential step for the production of a robust light response under physiological conditions. Here we present a novel mechanism to alleviate open channel block in the absence of depolarization by membrane lipid modulations. The results of this study show open channel block removal by membrane lipid modulations in both TRPL and NMDA channels of the photoreceptor cells and CA1 hippocampal neurons, respectively. Removal of open channel block is characterized by an increase in the passage-rate of the blocking cations through the channel pore. We propose that the profound effect of membrane lipid modulations on open channel block alleviation, allows the productions of a robust current in response to light in the absence of depolarization.

Key Words: TRP channels • Drosophila • photoreceptors • open channel block • NMDA channel • phospholipase C

Received for publication Sept. 8, 2008. Revision received Jan. 11, 2009. Accepted for publication Jan. 13, 2009.

Correspondence should be addressed to Baruch Minke, Department of Physiology, Faculty of Medicine, The Hebrew University, P. O. Box 12272, Jerusalem 91120, Israel. Email: minke{at}md.huji.ac.il

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