Acetylcholine Receptors in Model Membranes: Structure/Function Correlates.
Abstract
The nicotinic cholinergic receptor (AChR*) from Torpedo californica electric organ and the voltage sensitive sodium channel from rat brain were purified and thereafter reconstituted into lipid vesicles as well as into planar lipid bilayers. The reconstituted membrane displayed the biophysical, pharmacological and immunochemical properties characteristic of these channel proteins in vivo. A detailed kinetic analysis of channel gating demonstrated the existence of two channel open states. For acetylcholine (ACh), the typical values of the time constants of the short-lived and long-lived open states were about 0.5 ms and about 4 ms. The frequency of occurrence of the long-lived state increased with ACh concentration. The simplest interpretation is that both singly and doubly liganded states of the AChR undergo transitions to the open conformation. Channel opening was voltage dependent and favored by depolarization. Probability density analysis of dwell times in the open and closed states indicates the occurrence of one open state and several distinct closed states. The process of synaptic transduction as well as that of electric excitability has been reduced to studies on the molecular physiology of purified channel proteins in lipid bilayers. The stage is set to investigate how chemical and genetic modifications in the structure of these channel proteins affect their function. Keywords: Tetrodoxin; Sodium; potassium; Chlorine; Rubidium; Reaction kinetics; Electrophysiology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1985
- Accession Number
- ADA187704
Entities
People
- Mauricio Montal
Organizations
- University of California, San Diego