Modulation of proton-induced current fluctuations in the human nicotinic acetylcholine receptor channel
| Autor: | Christophe Danelon, Horst Vogel, Ruud Hovius, Jörg Grandl |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Slow-channel syndrome Patch-Clamp Techniques Protein Conformation Molecular Sequence Data Cholinergic Agents Analytical chemistry Biophysics Ion channel gating Ionizable site Gating Receptors Nicotinic Torpedo Transfection Models Biological Noise analysis Biochemistry Cell Line Membrane Potentials 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Amino Acid Sequence Ion channel 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug Chemistry Lysine Conductance Membrane hyperpolarization Cell Biology Markov Chains High-conductance state Kinetics Protein Subunits Nicotinic acetylcholine receptor Epibatidine Mutation Protons Current fluctuation 030217 neurology & neurosurgery Acetylcholine medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1768(1):76-89 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/j.bbamem.2006.07.015 |
| Popis: | The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that switches upon activation from a closed state to a full conducting state. We found that the mutation δ S268K, located at 12′ position of the second transmembrane domain of the δ subunit of the human nAChR generates a long-lived intermediate conducting state, from which openings to a wild-type like conductance level occur on a submillisecond time scale. Aiming to understand the interplay between structural changes near the 12′ position and channel gating, we investigated the influence of various parameters: different ligands (acetylcholine, choline and epibatidine), ligand concentrations, transmembrane voltages and both fetal and adult nAChRs. Since sojourns in the high conductance state are not fully resolved in time, spectral noise analysis was used as a complement to dwell time analysis to determine the gating rate constants. Open channel current fluctuations are described by a two-state Markov model. The characteristic time of the process is markedly influenced by the ligand and the receptor type, whereas the frequency of openings to the high conductance state increases with membrane hyperpolarization. Conductance changes are discussed with regard to reversible transfer reaction of single protons at the lysine 12′ side chain. |
| Databáze: | OpenAIRE |
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