Poster abstracts
Poster number 94 submitted by Micaiah McNabb
The role of small-conductance Ca2+ activated K+ channel, SK2, in astrocytic regulation of K+ in the brain
Micaiah McNabb (Neuroscience Graduate Program), Susma Timsina (Neuroscience Graduate Program), Yixing Du (Department of Neurosciences, University of California San Diego), Min Zhou
Abstract:
Astrocytes are effective regulators of extracellular potassium (K+) concentrations in the brain due to their unique equal capacity for K+ uptake and release. This is demonstrated across brain regions and model species by their characteristic ohmic, or passive, K+ conductance behavior. The molecular identities of all the leak-type K+ channels involved in generating this ohmic conductance, however, have remained unresolved. In neonatal astrocytes, the ohmic conductance can be attributed to the gap-junctional coupling connecting neighboring astrocytes within the shared syncytium, and all remaining leak conductance after blocking the gap junctions with 0.1 mM meclofenamic acid (MFA), can be suppressed with the application of 0.1 mM BaCl2, a selective blocker for inward-rectifying K+ channels (Kir). In mature astrocytes however, a significant portion of leak conductance persists following blockades of the gap junctions and Kir channels, indicating the presence of an additional leak-type K+ channel on the astrocyte membrane. Using quantitative PCR and immunohistochemistry to quantify mRNA and protein expression of several candidate leak-type K+ channels, we identified small-conductance Ca2+-activated K+ channel, SK2, as the most likely candidate. Whole-cell recordings from MFA-decoupled hippocampal astrocytes revealed a suppression of the passive conductance in response to 300 nM apamin, a highly selective SK channel blocker. Additionally, paired applications of apamin and BaCl2 resulted in the abolishment of passive conductance in mature astrocytes, confirming that Kir and SK channels are solely responsible for generating the ohmic conductance profile. This discovery will allow for future study into the role of astrocytic regulation of K+ in the brain and provide a potential therapeutic target for K+ dysregulation in disease.
Keywords: Astrocytes, Electrophysiology, Potassium