Cell-Specific Control of Neuronal Ion Channels: Function, Pharmacology, and Disease
Thursday, November 19, 2015
12:00 pm - 1:00 pm
LSRC - DIBS B035 Multipurpose Room
Diane Lipscombe, Interim Director, Brown Institute for Brain Science
Voltage-gated calcium ion (CaV) channels are critical for many biological functions. Among these, CaV channels control calcium entry that triggers neurotransmitter release from presynaptic terminals, rebound bursting in neurons, initial depolarizations that trigger action potential generation in excitable cells including neurons and heart, and excitation-dependent gene transcription. The work by Professor Lipscombe and her lab explores the cellular mechanisms that refine CaV channel properties - according to cell-type - for optimal control of cell function. She has focused on cell-specific control of mRNA processing and specifically cell-specific exon usage. Each major CaV gene family has the capacity to generate multiple, functionally different mRNAs and protein products. Professor Lipscombe's work shows the tissue and cell -specific expression patterns of isoforms and their distinct CaV channel biophysics, G protein sensitivities, and pharmacology. For example, variations arising from differential exon selection during CaV mRNA processing confer unique properties to CaV channel isoforms expressed in nociceptors in the pain pathway. CaV channels are the gatekeepers at junctions that separate noxious thermal signals, generated at the point of detection in the periphery, from central pain processing centers. Professor Lipscombe employed genetic manipulations to eliminate one of two possible splice isoforms of CaV expressed in nociceptors and demonstrated effects in vivo.