MODULATION AND REGULATION OF NEURONAL CALCIUM CHANNELS

Project Details

Description

The goal of this project is the examination of regenerative calcium
currents in central nervous system neurons grown in tissue culture and the
effects of catecholamines on these currents. Calcium-dependent action
potentials have been demonstrated in both central and peripheral vertebrate
neurons in the last few years. In molluscan nerve cells, heart tissue, and
peripheral nervous systems, some of the catecholamines have been found to
act by modifying the voltage dependent properties of the calcium channel.
Given the importance of catecholamines to normal brain function and their
implication in a variety of neurologic and psychiatric disorders, it is
critical to define the mechanism of action of these transmitters. Several
laboratories have suggested that in vertebrate neurons calcium action
potentials may be preferentially located on dendrites. Recently we have
demonstrated the presence of calcium spikes in mitral cells of the
olfactory bulb. These cells are a favorable system for the study of
calcium currents and their modulation since 1) they can be maintained in
dispersed cell tissue culture, 2) they have long dendrites which
participate in reciprocal synapses, and 3) the bulb contains many defined
populations of monoaminergic cells and terminals. Neurons from the
olfactory bulb of young rats will be used in this study.
Electrophysiological studies will proceed in two phases. In the first,
neurons will be penetrated with a single microeletrode and the presence and
characteristics of calcium dependent action potentials will be determined.
Catecholamines will then be added to the bath an/or iontophoresed directly
on the cells, and effects on the calcium dependent action potential will be
noted (e.g. rate of rise, duration, amplitude). In the second phase, the
newly developed technique of voltage clamping of excised patches of
membranes will be used to study the kinetic properties of the calcium
current in detail at a single or multiple channel level. It will then be
possible to study the modulation of this current by catecholamines at a
more basic level than has so far been possible.
StatusFinished
Effective start/end date12/31/896/30/01

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

ASJC

  • Medicine(all)
  • Neuroscience(all)
  • Cell Biology
  • Pharmacology

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