CHLORIDE CHANNELS IN HUMAN BRAIN

Project: Research project

Description

The ultimate goal of the proposed research project is to fully
characterize the ion channels that allow chloride ions to pass into and
out of rat and human cerebral cortical neurons. Most
electrophysiological research has focused on ion channels involved in the
transport of cations such as sodium, potassium, and calcium. It is now
clear that anion transport is at least as important to the normal and
pathological functions of cells as is the transport of cations and
therefor much research is needed to determine the basic mechanisms of the
proteins that allow Cl and other anions to pass into and out of cells.
Excitable cells, such as neurons and muscle, are especially sensitive to
anion fluxes as the movements of anions affects the excitability of these
cells and contributes to the integration of excitatory and inhibitory
signals impinging on these cells. The predominant non-transmitter
activated anion-selective ion channel present in neurons is the so-called
"fast" Cl channel, previously described in tissue-cultured rat skeletal
muscle, and recently discovered by this laboratory to be present at high
density in rat and human cerebral cortical neurons. In a previous study,
the kinetic activity of these channels was determined and the voltage
dependence was analyzed. The specific aims of the current proposal are
to (1) expand the discovery that these Cl channels are blocked, in a
voltage-dependent manner by the classical K channel blocker,
tetraethylammonium ion (TEA) and other quaternary ammonium (QA) ions (2)
study kinetic activity of Cl channels as low temperatures that facilitate
the resolution of the very rapid conformational rearrangements that the
ion channel proteins undergo during the ion transport process; (3)
determine the physiological role of fast Cl channels in the functioning
of neurons, and to confirm and expand upon the discovery that these
channels contribute to neuronal volume regulation and (4) to attempt to
clone the neuronal fast Cl channel using an oocyte expression assay. The
research proposed will significantly increase our knowledge about anion
transport channels in the nervous system and may lead to a better
understanding about how these channels are involved in the regulation of
neural functions in normal and pathological states.
StatusFinished
Effective start/end date12/1/9211/30/97

Funding

  • National Institutes of Health

Fingerprint

Chloride Channels
Anions
Neurons
Brain
Ion Channels
Cations
Research
Tetraethylammonium
Ion Transport
Ammonium Compounds
Nervous System
Oocytes
Potassium
Sodium
Ions
Calcium
Muscles
Temperature
Proteins

ASJC

  • Medicine(all)
  • Neuroscience(all)