- Brain Awareness Week
Regulation of voltage-gated Ca2+ channels
Our research centers on voltage-gated (Cav) Ca2+ channels and their roles in the nervous and cardiovascular systems. We view Cav channels as macromolecular complexes, the components of which regulate their properties and involvement in cellular transduction cascades. One focus is on Cav1 L-type channels at sensory “ribbon” synapses in the retina and inner ear, where Cav protein interactions transform presynaptic Ca2+ signals required for high-throughput neurotransmitter release. A second focus is on protein interactions regulate Cav1 channels involved in spontaneous firing (pacemaking) in the heart and brain. Our approach is multidisciplinary: we use patch-clamp electrophysiology for studies of Cav channel modulation and exocytosis; molecular biology, protein chemistry, and immuncytochemistry for analysis of Cav protein interactions; and gene silencing methods (siRNA, targeted gene disruption) and in vivo electrophysiology to evaluate the physiological consequences of Cav protein interactions in the context of hearing, vision, and cardiac rhythmicity. Our long-term goal is to develop pharmacological strategies to target cell-type and tissue-specific Cav regulatory mechanisms, which may prove more selective than current Cav agonists and antagonists in the treatment of neurological and cardiovascular disease.