Astrocytes are star-shaped cells that have long been functionally considered to provide structural, housekeeping and metabolic support to neurons in the central nervous system (CNS). This supposition has been based on the fact that astrocytes are not able to relay signals by means of electric impulses, as do neurons. However, astrocytes do exhibit membrane currents that are carried through poorly characterized potassium channels. Although these currents were discovered over 40 years ago, the nature of these channels remains largely unknown. This proposal is focused on determining whether astrocyte currents are carried through a a newly discovery potassium channel family, called two-pore domain potassium channels (2PKs). This project will further explore how changes in astrocyte 2PKs could modulate astrocyte homeostatic functions with consequent effect on neuronal function. Membrane ion channel currents from astrocytes will be measured in acute rat hippocampal slices measure. Potential astrocyte 2PKs will be further explored at the gene level by using single cell RT-PCR, and at the protein level by specific antibody labeling to post astrocytes using confocal immunocytochemistry. The functional impact of astrocytic 2PKs will be determined by silencing identified 2PKs using RNAi in the organotypic cultured hippocampus. These experiments will delineate the role of these channels and clarify the function of astrocytes in general. Since astrocytes play integral roles response of the nervous system to injury or disease, such knowledge has implications for human health as well as for the fundamental understanding of the nervous system.
The PI will provide opportunities for undergraduate, graduate, and postdoctoral students to participate in research on astrocytes. The broader impacts were judged as strong, particularly considering the PI is in an institute without ready access to undergraduate students.
