Dr. David McKinnon
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 in vivo.