Using Optical Probes To Study The Behavior Of Voltage Gated Ion Channels

Using Optical Probes to Study the Behavior of Voltage-gated Ion Channels

Handbook of Molecular-Genetic Techniques for Brain and Behavior Research

The book gives a broad overview of recombinant DNA techniques for the behavioral neuroscientist, with illustrative examples of applications. Species covered include rodents (mainly mice), Drosophila melanogaster, Caenorhabditis elegans and Danio rerio. Experimental techniques required to characterize the behavioral phenotypes of mutant animals is provided. Several aspects of novel molecular-genetic techniques are overviewed and possible research strategies are explained. The sections of the book start with general descriptions of techniques followed by illustrative examples. It is divided into six sections. Section 1, bioinformatics and genomics research. Section 2, top-down strategies, where the researcher starts with the phenotype and then analyzes the associated genes; bottom-up strategies, where the physiological chain leading to a phenotype is analyzed starting from the gene product. Section 3, transgenic approaches in rodents including overexpressing foreign genes and gene-targeting; systemic manipulation approaches directly targeting the central nervous system and methods used with invertebrates. Section 4, methods used to evaluate relevant behavioral phenotypes, including learning and aggression. Section 5, examples on molecular brain research in man. Section 6, ethical aspects of research in this field.

Mechanisms of ion channels voltage-dependency

Voltage-gated ion channels are transmembrane proteins in which at least one gate is controlled by the transmembrane potential. They are frequently very selectively permeable to sodium (Nav channels), potassium (Kv channels) or calcium (Cav channels) ions. Depending on the channels, opening of the activation gate is triggered by membrane depolarization (Kv, Nav and Cav channels) or hyperpolarization (HCN channels for instance). In addition, in many voltage-gated channels, a so-called inactivation gate is also present. Compared to the activation gate, the latter is oppositely coupled to the potential: In Kv, Nav and Cav channels, upon membrane depolarization, the inactivation gate closes whereas the activation gate opens. Depending on the cell types in which they are expressed and their physiological role, various voltage-dependent channels can be characterized by their conductance, ion selectivity, pharmacology and voltage-sensitivity. These properties are mainly dictated by the amino-acids sequence and structure of the pore forming subunit(s), presence of accessory subunit(s), membrane composition, intra- and extracellular ions concentration. Noteworthy, despite a profound variety of these ion channels characteristics, it seems that most of them obey to the same global, four-fold structure now obtained by several X-ray crystallography experiments. Given the wealth of electrophysiological, biochemical, optical, and structural data regarding ion channels voltage-dependency, we decided to put together in this e-book, up to date reviews describing the molecular details of these complex voltage-gated channels.