CALCIUM CURRENT POTENTIATION IN HIPPOCAMPAL NEURONS

Project Details

Description

The aim of this project is to examine the elementary properties of a
unique kind of calcium channel that responds to transient depolarizations
with long-lasting increases in activity. Interestingly, we have observed
this type of calcium channel activity in hippocampal neurons, but not in
neurons of the sympathetic ganglia, suggesting that this voltage-
dependent, long-term activation, or potentiation, may contribute to some
aspect of the complex synaptic plasticity that has been observed in the
hippocampus.

At present, too little is known about this channel to speculate on its
specific functions, although the possibilities are quite diverse, ranging
from enhanced neuronal excitability to regulation of gene expression. For
example, calcium channels of this type have been implicated in aging-
related learning deficits. It is, therefore, critical to determine the
precise biophysical characteristics of this potentiated activity under
standard and physiologically-relevant conditions to make comparisons with
other known calcium channel types and to gain insights into the effects
this activity would have on neurons in situ. Furthermore, by determining
how channel responsiveness is altered through the action of second
messenger systems and by learning whether specific neurotransmitters can
activate these same pathways in hippocampal neurons, important insights
into the dynamic regulation of this calcium channel potentiation can be
obtained. Moreover, by using a combination of kinetic modeling and
related experimental protocols, it will be possible to gain a fundamental
understanding of the mechanisms that underlie long-lasting calcium channel
activity.

To accomplish these goals, single-channel and whole-cell patch clamp
recordings will be made from hippocampal neurons. A variety of
stimulation protocols and recording conditions will be used to determine
the time course and voltage-dependence of the potentiated activity. In
addition, a collaborative effort to identify the molecular composition of
this calcium channel will be initiated during the time covered by this
grant application. By systematically studying a calcium channel with such
intriguing properties, we will establish the strong foundation necessary
to understand the functional role and clinical relevance of calcium
channel potentiation in the hippocampus.
StatusFinished
Effective start/end date9/1/958/31/99

Funding

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

ASJC

  • Genetics

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