Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
RNA editing modulates the binding of drugs and highly unsaturated fatty acids to the open pore of Kv potassium channels.
Decher N, Streit AK, Rapedius M, Netter MF, Marzian S, Ehling P, Schlichthörl G, Craan T, Renigunta V, Köhler A, Dodel RC, Navarro-Polanco RA, Preisig-Müller R, Klebe G, Budde T, Baukrowitz T, Daut J.
???displayArticle.abstract???
The time course of inactivation of voltage-activated potassium (Kv) channels is an important determinant of the firing rate of neurons. In many Kv channels highly unsaturated lipids as arachidonic acid, docosahexaenoic acid and anandamide can induce fast inactivation. We found that these lipids interact with hydrophobic residues lining the inner cavity of the pore. We analysed the effects of these lipids on Kv1.1 current kinetics and their competition with intracellular tetraethylammonium and Kvbeta subunits. Our data suggest that inactivation most likely represents occlusion of the permeation pathway, similar to drugs that produce 'open-channel block'. Open-channel block by drugs and lipids was strongly reduced in Kv1.1 channels whose amino acid sequence was altered by RNA editing in the pore cavity, and in Kv1.x heteromeric channels containing edited Kv1.1 subunits. We show that differential editing of Kv1.1 channels in different regions of the brain can profoundly alter the pharmacology of Kv1.x channels. Our findings provide a mechanistic understanding of lipid-induced inactivation and establish RNA editing as a mechanism to induce drug and lipid resistance in Kv channels.
Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971, Pubmed
Armstrong,
Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.
1971,
Pubmed Balsinde,
Phospholipase A(2) regulation of arachidonic acid mobilization.
2002,
Pubmed Beraud,
Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.
2006,
Pubmed Bhalla,
Control of human potassium channel inactivation by editing of a small mRNA hairpin.
2004,
Pubmed Bisogno,
Short- and long-term plasticity of the endocannabinoid system in neuropsychiatric and neurological disorders.
2007,
Pubmed Boland,
Polyunsaturated fatty acid modulation of voltage-gated ion channels.
2008,
Pubmed Brash,
Arachidonic acid as a bioactive molecule.
2001,
Pubmed Budde,
Different Types of Potassium Outward Current in Relay Neurons Acutely Isolated from the Rat Lateral Geniculate Nucleus.
1992,
Pubmed Calon,
Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model.
2004,
Pubmed Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed Connor,
Voltage clamp studies of a transient outward membrane current in gastropod neural somata.
1971,
Pubmed Darios,
Phospholipases and fatty acid signalling in exocytosis.
2007,
Pubmed Daut,
Modulation of the excitatory synaptic response by fast transient K+ current in snail neurones.
1973,
Pubmed Decher,
Structural basis for competition between drug binding and Kvbeta 1.3 accessory subunit-induced N-type inactivation of Kv1.5 channels.
2005,
Pubmed
,
Xenbase Decher,
Binding site of a novel Kv1.5 blocker: a "foot in the door" against atrial fibrillation.
2006,
Pubmed
,
Xenbase Decher,
Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2.
2008,
Pubmed Decher,
Molecular basis for Kv1.5 channel block: conservation of drug binding sites among voltage-gated K+ channels.
2004,
Pubmed
,
Xenbase De Petrocellis,
Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity.
2000,
Pubmed Farooqui,
Phospholipase A2-generated lipid mediators in the brain: the good, the bad, and the ugly.
2006,
Pubmed Fenwick,
Sodium and calcium channels in bovine chromaffin cells.
1982,
Pubmed Honoré,
External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids.
1994,
Pubmed Hoopengardner,
Nervous system targets of RNA editing identified by comparative genomics.
2003,
Pubmed Horn,
Channels get in an HUFA: RNA editing gets them out of a jam.
2010,
Pubmed Katona,
Endocannabinoid signaling as a synaptic circuit breaker in neurological disease.
2008,
Pubmed Koren,
Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells.
1990,
Pubmed
,
Xenbase Koschak,
Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom.
1998,
Pubmed Lundbaek,
Lipid bilayer-mediated regulation of ion channel function by amphiphilic drugs.
2008,
Pubmed Marcheselli,
Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression.
2003,
Pubmed Meves,
Arachidonic acid and ion channels: an update.
2008,
Pubmed Okamoto,
Biosynthetic pathways of the endocannabinoid anandamide.
2007,
Pubmed Oliver,
Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
2004,
Pubmed
,
Xenbase Panyi,
Probing the cavity of the slow inactivated conformation of shaker potassium channels.
2007,
Pubmed Patton,
RNA editing generates a diverse array of transcripts encoding squid Kv2 K+ channels with altered functional properties.
1997,
Pubmed Rettig,
Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
1994,
Pubmed
,
Xenbase Ryan,
Characterization of five RNA editing sites in Shab potassium channels.
2008,
Pubmed
,
Xenbase Schwid,
Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis.
1997,
Pubmed Stühmer,
Potassium channels expressed from rat brain cDNA have delayed rectifier properties.
1988,
Pubmed
,
Xenbase Trimmer,
Localization of voltage-gated ion channels in mammalian brain.
2004,
Pubmed Vennekamp,
Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators.
2004,
Pubmed Yellen,
The moving parts of voltage-gated ion channels.
1998,
Pubmed Zhou,
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.
2001,
Pubmed
,
Xenbase
