Membrane lipid modulations remove divalent open channel block from TRP-like and NMDA channels.
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.
Parnas
Moshe
M
Department of Physiology and the Kühne Minerva Center for Studies of Visual Transduction, Faculty of Medicine of The Hebrew University, Jerusalem 91120, Israel.
Katz
Ben
B
Lev
Shaya
S
Tzarfaty
Vered
V
Dadon
Daniela
D
Gordon-Shaag
Ariela
A
Metzner
Henry
H
Yaka
Rami
R
Minke
Baruch
B
D000818:Animals; D030801:Animals, Genetically Modified; D001703:Biophysics; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008027:Light; D019787:Linoleic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008563:Membrane Lipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D008563:Membrane Lipids; D016194:Receptors, N-Methyl-D-Aspartate; D050051:Transient Receptor Potential Channels; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D019787:Linoleic Acid; D008274:Magnesium; D002118:Calcium