Assistant: Christine Goldsberry
Assistant Email: firstname.lastname@example.org
Assistant Phone: 615-936-0277
Education & Training
PhD, Physiology, The University of London, St. George's Medical School, United Kingdom (1994)
BSc, Pharmacology, The University of Edinburgh, Scotland (1990)
Regulation of Ion Channels, Calcium Signaling and Neurotransmitter Release Calcium is an important intracellular messenger that regulates many diverse cellular events including gene expression, enzyme activity, membrane excitability, learning and memory, muscle contraction and neurotransmitter / hormone release. One of the main routes for calcium entry into excitable cells is through voltage-gated calcium channels (Ca-channels).
Consequently, these Ca-channels play a pivotal role in many cellular functions including the triggering and regulation of neurotransmitter/hormone release. Changes in the efficacy of neurotransmitter release shape the processing and transfer of information by neurons and thus influence many aspects of neuronal physiology including memory formation and complex behavioral responses. Indeed, Ca-channel mutations are associated with several neurological disorders and some neuropharmacological agents modulate Ca-channel function. Therefore, a better understanding of Ca-channel operation and transmitter release mechanisms is required to advance current models of neuronal signaling in physiological and pathophysiological conditions.
My lab studies the properties and regulation Ca-channels and the control of transmitter release from neurosecretory cells. We use a variety of techniques including, patch clamp electrophysiology, fluorescent imaging of intracellular calcium levels, and electrochemical detection of transmitter release from individual cells using carbon fiber amperometry. We use a variety of cells and cell lines for these investigations including adrenal chromaffin cells, a widely used neurosecretory model. Unlike most presynaptic terminals, chromaffin cells are accessible to patch clamp techniques. Using chromaffin cells we can detect the fusion and release of individual vesicles of transmitter (using amperometry) and directly correlate secretion with detailed analysis of Ca-channel physiology. The catecholamines released from chromaffin cells play a major role in the response to stress or danger, so the study of ion channels and transmitter release mechanisms in these cells is physiologically important per se, and also provides an excellent model of presynaptic transmitter release.
We also study heterologously expressed Ca-channels. This enables us to control the subunit composition of the channels and to investigate targeted mutations and splice variants that may contribute to neurological disorders and channelopathies. Current projects in the lab are focused on 1) the role of Ca-channel inactivation in the control transmitter release during physiological stimuli. 2) G-protein mediated regulation of Ca-channels. 3) the regulation of transmitter release by direct G-protein subunit binding to the exocytotic machinery (in collaboration with Dr Heidi Hamm’s lab in the Dept of Pharmacology).
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