Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;99(3):914-926.
doi: 10.1002/jnr.24749. Epub 2020 Dec 4.

Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine-induced status epilepticus

Li Zhou  1 , Weixing Xu  1 , Dong An  1 , Sha Sha  1 , Chen Men  2 , Yingchun Li  1 , Xiaoli Wang  1 , Yimei Du  3 , Lei Chen  1   4
Affiliations

Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine-induced status epilepticus

Li Zhou et al. J Neurosci Res. 2021 Mar.

Abstract

Activation of transient receptor potential vanilloid 4 (TRPV4) can increase hippocampal neuronal excitability. TRPV4 has been reported to be involved in the pathogenesis of epilepsy. Voltage-gated potassium channels (VGPCs) play an important role in regulating neuronal excitability and abnormal VGPCs expression or function is related to epilepsy. Here, we examined the effect of TRPV4 activation on the delayed rectifier potassium current (IK ) in hippocampal pyramidal neurons and on the Kv subunits expression in male mice. We also explored the role of TRPV4 in changes in Kv subunits expression in male mice following pilocarpine-induced status epilepticus (PISE). Application of TRPV4 agonists, GSK1016790A and 5,6-EET, markedly reduced IK in hippocampal pyramidal neurons and shifted the voltage-dependent inactivation curve to the hyperpolarizing direction. GSK1016790A- and 5,6-EET-induced inhibition of IK was blocked by TRPV4 specific antagonists, HC-067047 and RN1734. GSK1016790A-induced inhibition of IK was markedly attenuated by calcium/calmodulin-dependent kinase II (CaMKII) antagonist. Application of GSK1016790A for up to 1 hr did not change the hippocampal protein levels of Kv1.1, Kv1.2, or Kv2.1. Intracerebroventricular injection of GSK1016790A for 3 d reduced the hippocampal protein levels of Kv1.2 and Kv2.1, leaving that of Kv1.1 unchanged. Kv1.2 and Kv2.1 protein levels as well as IK reduced markedly in hippocampi on day 3 post PISE, which was significantly reversed by HC-067047. We conclude that activation of TRPV4 inhibits IK in hippocampal pyramidal neurons, possibly by activating CaMKII. TRPV4-induced decrease in Kv1.2 and Kv2.1 expression and IK may be involved in the pathological changes following PISE.

Keywords: Kv subunit expression; RRID: SCR_003070 (ImageJ software); RRID: SCR_012763 (STATA software); RRID:AB_10673392 (Kv2.1 antibody); RRID:AB_2040144 (Kv1.1 antibody); RRID:AB_2313792 (Kv1.2 antibody); RRID:AB_2630358 (GAPDH antibody); hippocampus; pilocarpine-induced status epilepticus; transient receptor potential vanilloid 4; voltage-gated potassium channel.

PubMed Disclaimer

References

REFERENCES

    1. Antonucci, D. E., Lim, S. T., Vassanelli, S., & Trimmer, J. S. (2001). Dynamic localization and clustering of dendritic Kv2.1 voltage-dependent potassium channels in developing hippocampal neurons. Neuroscience, 108, 69-81. https://doi.org/10.1016/s0306-4522(01)00476-6
    1. Chen, L., Liu, C., & Liu, L. (2008). The modulation of voltage-gated potassium channels by anisotonicity in trigeminal ganglion neurons. Neuroscience, 154, 482-495. https://doi.org/10.1016/j.neuroscience.2008.03.046
    1. Chen, L., Liu, C., Liu, L., & Cao, X. (2009). Changes in osmolality modulate voltage-gated sodium channels in trigeminal ganglion neurons. Neuroscience Research, 64, 199-207. https://doi.org/10.1016/j.neures.2009.02.012
    1. Chen, X., Sun, F., Wei, Y., Wang, L., Zang, Z., Chen, B., & Yang, H. (2016). Increased expression of transient receptor potential vanilloid 4 in cortical lesions of patients with focal cortical dysplasia. CNS Neuroscience & Therapeutics, 22(4), 280-290. https://doi.org/10.1111/cns.12494
    1. Chen, X., Yang, M., Sun, F., Liang, C., Wei, Y., Wang, L., Yue, J., Chen, B., Li, S., Liu, S., & Yang, H. (2016). Expression and cellular distribution of transient receptor potential vanilloid 4 in cortical tubers of the tuberous sclerosis complex. Brain Research, 1636, 183-192. https://doi.org/10.1016/j.brainres.2016.02.012

Publication types

MeSH terms

Substances

LinkOut - more resources