The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments
Year: 2013
Type: article
Abstract: TWIK-1 two-pore domain K(+) channels are expressed abundantly in astrocytes. In the present study, we examined the extent to which TWIK-1 contributes to the linear current-voltage (I-V) relationship (passive) K(+) membrane conductance, a dominant electrophysiological feature of mature hippocampal astrocytes. Astrocytes from TWIK-1 knockout mice have a more negative resting potential than those from wild type animals and a reduction in both inward rectification and Cs(+) permeability. Nevertheless, the overall whole-cell passive conductance is not altered significantly in TWIK-1 knockout astrocytes. The expression of Kir4.1 and TREK-1, two other major astrocytic K(+) channels, or of other two-pore K(+) channels is not altered in TWIK-1 knockout mice, suggesting that the mild effect of TWIK-1 knockout does not result from compensation by these channels. Fractionation experiments showed that TWIK-1 is primarily localized in intracellular cytoplasmic fractions (55%) and mildly hydrophobic internal compartment fractions (41%), with only 5% in fractions containing plasma membranes. Our study revealed that TWIK-1 proteins are mainly located in the intracellular compartments of hippocampal astrocyte under physiological condition, therefore a minimal contribution of TWIK-1 channels to whole-cell currents is likely attributable to a relatively low level presence of channels in the plasma membrane.
Institutions: The Ohio State University Wexner Medical Center, The Ohio State University, University of South Carolina, University at Albany, State University of New York, Yale University, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Université Nice Sophia Antipolis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W1967902520