G Protein Coupled Receptors, Phosphoinositide Lipids, and Ion Channels Control Membrane Excitability
Stream Seminar Video
Ion channel function and electrical excitability are modulated by hormones and neurotransmitters acting on G-protein coupled receptors. Intracellular cyclic nucleotides and calcium are common intermediaries after receptor activation. We found two others: first, fast release of Gβγ subunits from G proteins and second, a slower depletion of the plasma membrane phosphoinositide lipid PI(4,5)P2. This lipid is a cofactor for many plasma membrane ion channels. As biophysicists, we have studied and modeled the dynamics of G-protein signaling. The lipid connection made us interested in the pools of cellular phosphoinositides, their location, their perturbation by receptors, subcellular trafficking, and actions. All these properties affect the dynamics of electrical excitability and ultimately both homeostasis and changeability of nerve circuits and cardiac and smooth muscle.
Wayne E. Crill Endowed Professor, Physiology & Biophysics, University of Washington Author of Ion Channels of Excitable Membranes, 3rd Ed.