Professor of Neurobiology & Behavior
We are interested in how the electrophysiological phenotype of excitable
cells is established and maintained in vivo. We believe that electrophysiological
phenotype is actively maintained by a combination of physiological inputs
and trophic signals and consequently, can be modified by changes in
the nature of these inputs. This plasticity allows an excitable cell
to adapt to the changing demands of the physiological processes that
it must perform.
To study this problem it is first necessary to identify the channels
that control electrophysiological phenotype and subsequently identify
the genes that encode these channels. Ultimately we wish to identify
the physiological signals that regulate channel gene expression in vivo.
For most of our studies we have concentrated on voltage-gated potassium
channels since the primary function of most of these channels is to
control the electrical properties of excitable cells.
We currently study two questions that are of importance for cardiovascular
function. The first problem that we are trying to understand is how
gradients of ion channel expression are established within the heart.
Cardiac myocytes express different complements of ion channels depending
upon their location within the heart. One particularly striking phenomena
is the gradient of transient outward current expression across the ventricular
wall. This gradient is important in establishing the appropriate sequence
of depolarization and subsequent repolarization within the heart which
co-ordinates the correct sequence of ventricular contraction and relaxation.
We are interested in understanding the molecular basis of this gradient
and determining the physiological signals that establish the gradient.
We study an analogous problem in the sympathetic nervous system. Peripheral
sympathetic neurons have firing properties that are differentiated depending
upon their function within the sympathetic system. Neurons involved
in vasoconstriction have a different electrophysiological phenotype
to those that control other physiological functions even though all
sympathetic neurons arise from a common set of precursor cells. It appears
that the electrophysiological phenotype of sympathetic neurons is established
by physiological cues and there is evidence that pathophysiological
events such as hypertension can induce changes in the electrophysiological
phenotypes of vasoconstrictor neurons. We are attempting to determine
how the electrophysiological phenotype of sympathetic neurons is established