They are generally closed in resting neurons, but open transiently in response to changes in the membrane potential or in response to synaptically released neurotransmitters. The complex electrical signals generated by neurons involves the coordinated opening of many different types of channels during excitation. We are studying the cellular and molecular mechanisms by which neuronal ion channel activity can be modified by specific neurotransmitter and drug molecules.
Experimental work uses biophysical techniques to understand the underlying kinetic mechanisms.
A major focus of our work is understanding the mechanism of modulation of voltage-gated calcium channels. Calcium channels play a central role in many neuronal processes including the release of neurotransmitters by exocytosis, axon outgrowth, gene expression, and neuronal survival. There are many different types of voltage-gated calcium channel in the brain that are derived from at least five gene families. Although calcium channels open within milliseconds following membrane depolarization, their expression and activity is highly regulated over a time span of minutes, hours, and days. One project has focused on the modulatory actions of glutamate, the main excitatory neurotransmitter in the brain.