Voltage-gated calcium (Ca) channels serve two major roles, an electrogenic role by passing current and thereby affecting membrane potential and a regulatory role because they are selectively permeable to Ca, an important signaling molecule. Changes in global intracellular and local Ca concentrations lead to the activation of Ca dependent proteins and channels and thereby control diverse cell processes including membrane excitability, cell death, growth, vesicular release, and synaptic plasticity. Regulation of Ca is, therefore, critical and disruption of this regulation is pathophysiological.

T-type Ca channels, one family of voltage-gated Ca channels, are widely expressed in the brain. They serve both an electrogenic and regulatory role in that they contribute to low threshold Ca spikes, pacemaking, rebound burst firing as well as producing a steady Ca influx near the resting membrane potential and low amplitude Ca oscillations. They have been implicated in several neurological disorders including but not limited to absence seizures, neurogenic pain, sleep disorders, and ataxia.

I am specifically interested in understanding permeation through these channels in an effort to better understand how they can participate in cellular physiologies and pathophysiologies.  I use both single channel and whole cell electrophysiological techniques to study the permeation through these channels under different ionic conditions as well as site-directed mutagenesis to understand how different residues determine the characteristic permeation properties of these channels.