The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, KCNK3, Is Regulated By 14-3-3beta-Dependent, PKC-Mediated Endocytic Trafficking

Student Author(s)

Luke Gabriel

Academic Program


UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Department of Microbiology and Physiological Systems; Department of Psychiatry

Publication Date


Document Type



Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology


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 protein levels or ablating the endocytic motif completely abrogated PKC-regulated KCNK3 trafficking. These results demonstrate that neuronal potassium leak channels are not static membrane residents, but are subject to 14-3-3beta-dependent regulated trafficking, providing a straightforward mechanism to modulate neuronal excitability and synaptic plasticity by Group I mGluRs.

DOI of Published Version



J Biol Chem. 2012 Jul 30. DOI 10.1074/jbc.M112.391458. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID