Abstract
We have recently shown that a linear current-to-voltage (I-V) relationship of membrane conductance (passive conductance) reflects the intrinsic property of K+ channels in mature astrocytes. While passive conductance is known to underpin a highly negative and stable membrane potential (VM) essential for the basic homeostatic function of astrocytes, a complete repertoire of the involved K+ channels remains elusive. TREK-1 two-pore domain K+ channel (K2P) is highly expressed in astrocytes, and covalent association of TREK-1 with TWIK-1, another highly expressed astrocytic K2P, has been reported as a mechanism underlying the trafficking of heterodimer TWIK-1/TREK-1 channel to the membrane and contributing to astrocyte passive conductance. To decipher the individual contribution of TREK-1 and address whether the appearance of passive conductance is conditional to the co-expression of TWIK-1/TREK-1 in astrocytes, TREK-1 single and TWIK-1/TREK-1 double gene knockout mice were used in the present study. The relative quantity of mRNA encoding other astrocyte K+ channels, such as Kir4.1, Kir5.1, and TREK-2, was not altered in these gene knockout mice. Whole-cell recording from hippocampal astrocytes in situ revealed no detectable changes in astrocyte passive conductance, VM, or membrane input resistance (Rin) in either kind of gene knockout mouse. Additionally, TREK-1 proteins were mainly located in the intracellular compartments of the hippocampus. Altogether, genetic deletion of TREK-1 alone or together with TWIK-1 produced no obvious alteration in the basic electrophysiological properties of hippocampal astrocytes. Thus, future research focusing on other K+ channels may shed light on this long-standing and important question in astrocyte physiology.
Highlights
Mature hippocampal astrocytes exhibit a membrane K+ conductance characterized by a linear current-to-voltage (IV) relationship, and a highly negative membrane potential (VM) (Zhou et al, 2006; Kafitz et al, 2008)
We have previously shown that TWIK-1 proteins are mainly located in the intracellular compartments of hippocampal astrocytes (Wang et al, 2013), whereas the subcellular distribution of TREK-1 in hippocampal astrocytes is yet unknown
We show that the VM was comparable between the two experimental groups: −75.9 ± 0.17 mV (n = 103) in wild type (WT) vs. −75.7 ± 0.18 mV (n = 94) in TWIK-1−/−/TREK-1−/− astrocytes (P > 0.05; Figure 5A), indicating a TWIK-1/TREK-1 heterodimer is not required for the highly negative VM that is critical for the homeostatic function of astrocytes (Figure 5A)
Summary
Mature hippocampal astrocytes exhibit a membrane K+ conductance characterized by a linear current-to-voltage (IV) relationship (passive conductance), and a highly negative membrane potential (VM) (Zhou et al, 2006; Kafitz et al, 2008). Both of these electrophysiological features are fundamental for the basic homeostatic functions of astrocytes in the brain (Verkhratsky and Steinhauser, 2000; Walz, 2000; Olsen and Sontheimer, 2008; Wang and Bordey, 2008; Kimelberg, 2010). TWIK-1 gene knockout affected the passive conductance minimally because of the retention of large amounts of TWIK-1 channels in intracellular compartments and the behavior of this channel as a non-selective cation channel in the membrane (Wang et al, 2013, 2015)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
