Ion Channel Regulation By Signal Transduction Pathways

Environmental Health Sciences

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Abstract

Summary of Work: In the Membrane Signaling Group, we study the signal transduction pathways which regulate cell function without altering gene expression. Ion channel proteins are the effectors for many of these pathways, regulating electrical signaling in the brain, hormone secretion, cardiovascular contractility, epithelial transport, and cell migration. Inherited mutations in channel encoding genes are responsible for many serious human diseases. We focus on the signaling pathways linking G protein coupled receptors to ion channel regulation through calcium and reversible protein phosphorylation. The patch clamp technique allows us to measure the activity of individual channel proteins in real time in situ in live cells. We have discovered that G proteins stimulate potassium channels through protein phosphatases, which are the targets of many aquatic microbial toxins. In particular we have identified the molecular basis for regulation of calcium- and voltage-activated potassium channels by reversible protein phosphorylation. In addition we have identified a new G protein dependent signaling mechanism for thyroid hormone, which could explain its importance for neural development.