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Neuroscience and Neurobiology

Haley Melikian

Nerve Tissue Proteins

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The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, Kcnk3, Is Regulated By 14-3-3beta-Dependent, Pkc-Mediated Endocytic Trafficking, Luke Gabriel, Anatoli Lvov, Demetra Orthodoxou, Ann Rittenhouse, William Kobertz, Haley Melikian Feb 2015

The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, Kcnk3, Is Regulated By 14-3-3beta-Dependent, Pkc-Mediated Endocytic Trafficking, Luke Gabriel, Anatoli Lvov, Demetra Orthodoxou, Ann Rittenhouse, William Kobertz, Haley Melikian

Haley Melikian

The acid-sensitive neuronal potassium leak channel, KCNK3, is vital for setting the resting membrane potential and is the primary target for volatile anesthetics. Recent reports demonstrate that KCNK3 activity is downregulated by PKC; however, the mechanisms responsible for PKC-induced KCNK3 downregulation are undefined. Here, we report that endocytic trafficking dynamically regulates KCNK3 activity. Phorbol esters and Group I mGluR activation acutely decreased both native and recombinant KCNK3 currents with concomitant KCNK3 surface losses in cerebellar granule neurons and cell lines. PKC-mediated KCNK3 internalization required the presence of both 14-3-3beta and a novel potassium channel endocytic motif, as depleting either 14-3-3beta …