Ion Channel Modulation, Protein Phosphorylation, and Signal Transduction.
Ion channels regulate the movement of ions across plasma membranes, a process which underlies electrical signaling and provides the basis for muscle contraction, synaptic transmission, and secretion. In our laboratory, we investigate the modulation of ion channels, particularly by phosphorylation and second messengers. Our recent studies are focusing on the function of mitochondrial ATP-sensitive potassium channels (mKATP) because they can mediate a protective response during oxidative stress. Our data has shown that the opening of mKATP releases reactive oxygen species from mitochondria which then activate p38 mitogen-activated protein kinase (p38 MAPK) (see Figure). Our research goals are to identify the cellular mechanisms that lead to mKATP opening and to characterize downstream components of the protective process. In the long term, this research may help in the development of drugs that can protect the heart and brain against cell death during periods of ischemia.
We also study the role of p38 MAPK activation in other tissues. We recently reported that p38 MAPK activation induced fetal hemoglobin in erythroid cells. This finding has the potential to aid in treatment protocols in the management of sickle cell disease. In summary, we are investigating the pivotal role of mKATP regulation in cellular adaptations that promote cell survival during stress.
Ion Channel Modulation, Signal Transduction, and MAPKs.
