Anti-hypoxic effect of interleukin-10 in hippocampal neurons is mediated by modulation of TASK-1 and TASK-3 channels activity.
- Resource Type
- Article
- Authors
- Konakov, Maxim V.; Teplov, Ilia Y.; Levin, Sergey G.; Nenov, Miroslav N.
- Source
- Biochemical & Biophysical Research Communications. Jul2022, Vol. 615, p17-23. 7p.
- Subject
- *POTASSIUM channels
*INTERLEUKIN-10
*NEURONS
*HIPPOCAMPUS (Brain)
*STRAY currents
*PHOSPHATIDYLINOSITOL 3-kinases
- Language
- ISSN
- 0006-291X
It has been shown that anti-inflammatory cytokine interleukin-10 (IL-10) can exert anti-hypoxic effect preventing post-hypoxic neuronal hyperexcitability. Yet, exact mechanisms of IL-10 mediated anti-hypoxic action on neuronal function are not fully understood. We suggested that IL-10 can exert its anti-hypoxic action via modulation of activity of two-pore potassium TASK-1 and TASK-3 channels. To study the involvement of TASK-1 and TASK-3 channels we employed a combination of whole-cell patch clamp and pharmacological inhibitory analysis to assess if IL-10 and brief hypoxic episode can modulate K+ background leak current (I leak) and membrane input resistance (R in) in cultured hippocampal neurons. We found that IL-10 in a dose-dependent manner can significantly increase I leak with concomitant reduction in R in. Neurons that were exposed to brief hypoxic episode on contrary showed significant decrease in I leak with concomitant increase in R in. Pretreatment with IL-10 prior hypoxic episode was able to abolish negative effect of hypoxia on I leak and R in. IL-10 potentiating action on I leak and R in was occluded by co-addition of selective blockers of TASK-1 and TASK-3 channels – ML365 and PK-THPP. Co-addition of LY294002, an inhibitor of PI3-kinase occluded IL-10 action on I leak and R in showing involvement of PI3K-associated pathway in IL-10 mediated regulation of TASK channel function. Our results provide new insights into IL-10 mediated neuroprotective and anti-hypoxic actions showing TASK-1 and TASK-3 channels as downstream targets of this anti-inflammatory cytokine. • IL-10 potentiates background I leak and reduces R in. • IL-10 and brief hypoxic episode modulate TASK-1 and TASK-3 channels activity. • TASK-1 and TASK-3 channels are targets of in IL-10 anti-hypoxic effects. • PI3K signaling pathway involved in IL-10 effects on TASK-1 and TASK-3 channels. [ABSTRACT FROM AUTHOR]