TY - JOUR

T1 - Illuminating the structure and function of Cys-loop receptors

AU - Pless, Stephan Alexander

AU - Lynch, Joseph W

PY - 2008/10

Y1 - 2008/10

N2 - Cys-loop receptors are an important class of ligand-gated ion channels. They mediate fast synaptic neurotransmission, are implicated in various 'channelopathies' and are important pharmacological targets. Recent progress in X-ray crystallography and electron microscopy has provided a considerable insight into the structure of Cys-loop receptors. However, data from these experiments only provide 'snapshots' of the proteins under investigation. They cannot provide information about the various conformations the protein adopts during transition from the closed to the open and desensitized states. Voltage-clamp fluorometry helps overcome this problem by simultaneously monitoring movements at the channel gate (through changes in current) and conformational rearrangements in a domain of interest (through changes in fluorescence) in real time. Thus, the technique can provide information on both transitional and steady state conformations and serves as a real time correlate of the channel structure and its function. Voltage-clamp fluorometry experiments on Cys-loop receptors have yielded a large body of data concerning the mechanisms by which agonists, antagonists and modulators act on these receptors. They have shed new light on the conformational mobility of both the ligand-binding and the transmembrane domain of Cys-loop receptors.

AB - Cys-loop receptors are an important class of ligand-gated ion channels. They mediate fast synaptic neurotransmission, are implicated in various 'channelopathies' and are important pharmacological targets. Recent progress in X-ray crystallography and electron microscopy has provided a considerable insight into the structure of Cys-loop receptors. However, data from these experiments only provide 'snapshots' of the proteins under investigation. They cannot provide information about the various conformations the protein adopts during transition from the closed to the open and desensitized states. Voltage-clamp fluorometry helps overcome this problem by simultaneously monitoring movements at the channel gate (through changes in current) and conformational rearrangements in a domain of interest (through changes in fluorescence) in real time. Thus, the technique can provide information on both transitional and steady state conformations and serves as a real time correlate of the channel structure and its function. Voltage-clamp fluorometry experiments on Cys-loop receptors have yielded a large body of data concerning the mechanisms by which agonists, antagonists and modulators act on these receptors. They have shed new light on the conformational mobility of both the ligand-binding and the transmembrane domain of Cys-loop receptors.

KW - Animals

KW - Cysteine

KW - Fluorometry

KW - Humans

KW - Ion Channel Gating

KW - Ion Channels

KW - Membrane Proteins

KW - Patch-Clamp Techniques

U2 - 10.1111/j.1440-1681.2008.04954.x

DO - 10.1111/j.1440-1681.2008.04954.x

M3 - Journal article

C2 - 18505452

VL - 35

SP - 1137

EP - 1142

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 10

ER -