A fundamental property of neuronal electrical activity
is that this activity is subject to modulation in
response to numerous neurotransmitters, peptides and
other signaling molecules. Dr. Reinhart's lab is studying
the molecular mechanisms by which ion channels are
subject to neuromodulation. Their focus is on a model
of ion channel regulatory complexes which predicts
that some ion channels are tightly associated with
other proteins such as protein kinases, phosphatases,
or other ion channels.
Such protein complexes are targets for numerous second
messengers and other signaling molecules including
Ca2+ and G-proteins. Dr. Reinhart and his
colleagues are examining how such ion channel protein
complexes can integrate and store information originating
from extracellular signals. To address these questions
they use a multi-disciplinary approach embracing both
electrophysiological and molecular biological tools.
General approaches used include protein-level studies
of K+ channels, the reconstitution of ion channels
into planar lipid bilayers,structure-function studies
of K+ channels expressed in Xenopus oocytes and mammalian
cell lines, and channel recordings from neurons in
brain slices.
Projects currently underway include the structure/function
studies on Ca2+-activated K+ channels and
associated proteins from human brain, biochemical
studies examining how protein complexes assemble,
electrophysiological studies examining how signaling
molecules such as Ca2+ and protein kinases
modulate the activity of single ion channels, studying
the emergent properties of channels due to the sequential
phosphorylation of channels at multiple sites, and
analyzing the contribution of individual ion channel
types in well studied forms of neuronal plasticity
such as long-term depression (LTD). The relationship
between ion channel defects and human diseases is
also being studied, particularly in the context of
Ataxia telangiectasia.
