|
|
Research
Ion Channel Signaling Complexes in Mammalian Nervous System and Muscle Neurons and other excitable cells have the unique ability to transmit and to respond to signals on a millisecond time scale. These rapid signals are due to ion channels, which are the molecular gates that control electrical activity. Our research focuses on potassium channels and the signal transduction complexes that are involved in the regulation and trafficking of ion channels. Our primary efforts are directed towards understanding the molecular mechanisms underlying the function of inwardly rectifying potassium channels. Potassium channels constitute more than 75 human genes, making them the most abundant and diverse group of ion channel in the human genome, and also the most important for regulating cellular electrical signals. Potassium channels are key components responsible for the control of cell excitability in neurons, cardiac and skeletal muscle, and pancreatic ß cells. As a result, they play a crucial role in electrical firing in the nervous system, generation of the heart beat, contraction of muscles, and secretion of hormones. The central role of the inward rectifier potassium channels in the electrical properties of neurons, glia and muscle cells makes them of particular importance in understanding electrical activity in the brain and heart. In addition, inward rectifiers are pharmacological targets for control of insulin release from the pancreas, control of cardiac arrhythmia, and regulation of hypertension. Our work is focused broadly in two areas: (i) investigation of channel trafficking, localization and regulation by channel-associated signaling complexes, and (ii) structure/function studies to determine the molecular mechanisms by which these channels provide their unique functions. Recently we have used a proteomics approach to identify complexes of signaling proteins that are associated with the channels. This work revealed over 20 signaling/trafficking proteins in several complexes that associate with inward rectifier potassium channels. Using channel expression in mammalian neurons, glial, muscle cells and epithelial cells, both in culture and in vivo, we are examining the role of the channel-associated signaling complexes. Our studies encompass a variety of methods including cell biology, molecular biology, confocal and immunofluorescence imaging, biochemical studies of trafficking, protein-protein interaction and surface expression, and biophysical/electrophysiological studies of electrical activity. Using a combination of molecular biological and biophysical approaches, our goal is to learn how molecular events shape the electrical signals and responses of the nervous system. |
|
Home | Members | Research | Publications | Links MCDB Website | Vandenberg Faculty Website
Vandenberg Lab • Molecular, Cellular, and Developmental Biology |
