Insights into the outward K+ currents-based gating mechanism of GIRK2 channel

Rui Wang; Yan Lu; Dailin Li

doi:10.1117/12.2673594

4 April 2023 Insights into the outward K⁺ currents-based gating mechanism of GIRK2 channel

Rui Wang, Yan Lu, Dailin Li

Proceedings Volume 12603, Biophysical Society of GuangDong Province Academic Forum: Precise Photons and Life Health (PPLH 2022); 126030J (2023) https://doi.org/10.1117/12.2673594
Event: 2022 Biophysical Society of Guang Dong Province Academic Forum - Precise Photons and Life Health (PPLH 2022), 2022, Guangzhou, China

Abstract

GIRK channels have been involved in numerous physiological functions by regulating cellular excitability. Considering the characteristics of inward rectification, structure activity relationships of GIRK channels have been studied extensively based on the inward movements of ions. In contrast, the outward K⁺ currents based gating mechanism remains to be investigated in depth, although some drug molecules (dofetilide, cromakalim, and pinacidil etc.) exert medical effects by the current block or activation. In this study, the all-atom microsecond-scale molecular dynamics method was employed to explore the outward currents based gating mechanism of the GRK2 channels, which were modulated by different factors (Na⁺, Gβγ, and Na⁺-Gβγ). The results show that the Na⁺ and Gβγ subunits work together to activate the GIRK2 channel, in which Na⁺ predominantly regulates the G-loop gate, while Gβγ subunits mainly regulate the HBC gate. Our findings provide structural insights into the gating mechanism of GIRK channels and help to understand the pathology and pharmacodynamics mechanisms of drugs related to outflow currents.

Citation Download Citation

Rui Wang, Yan Lu, and Dailin Li "Insights into the outward K⁺ currents-based gating mechanism of GIRK2 channel", Proc. SPIE 12603, Biophysical Society of GuangDong Province Academic Forum: Precise Photons and Life Health (PPLH 2022), 126030J (4 April 2023); https://doi.org/10.1117/12.2673594

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