BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke

Shuxian Huang; Tingting Chen; Qian Suo; Rubing Shi; Haroon Khan; Yuanyuan Ma; Yaohui Tang; Guo-Yuan Yang; Zhijun Zhang

doi:10.3389/fncel.2021.683769

BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke

Front Cell Neurosci. 2021 Jul 1:15:683769. doi: 10.3389/fncel.2021.683769. eCollection 2021.

Authors

Shuxian Huang¹, Tingting Chen¹, Qian Suo¹, Rubing Shi¹, Haroon Khan¹, Yuanyuan Ma^{1

2}, Yaohui Tang¹, Guo-Yuan Yang^{1

2}, Zhijun Zhang¹

Affiliations

¹ Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
² Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Microglial phagocytosis benefits neurological recovery after stroke. Large-conductance Ca2⁺-activated K⁺ currents are expressed in activated microglia, and BK channel knockout aggravates cerebral ischemic injury. However, the effect of BK channels on microglial phagocytosis after ischemic stroke remains unknown. Here, we explored whether BK channel activation is beneficial for neurological outcomes through microglial phagocytosis after ischemic stroke. ICR mice after transient middle cerebral artery occlusion (tMCAO) were treated with dimethyl sulfoxide (DMSO), BK channel activator NS19504, and inhibitor Paxilline. The results showed a decrease in BK channel expression after tMCAO. BK channel activator NS19504 alleviates neurological deficit after experimental modeling of tMCAO in mice compared to the control. Furthermore, we treated primary microglia with DMSO, NS19504, and Paxilline after oxygen glucose deprivation (OGD). NS19504 promoted primary microglial phagocytosing fluorescent beads and neuronal debris, which reduced neuronal apoptosis after stroke. These effects could be reversed by BK channel inhibitor Paxilline. Finally, NS19504 increased relative phosphorylated extracellular signal-regulated kinase 1/2 expression compared to the Paxilline group at the third day after stroke. Our findings indicate that microglial BK channels are a potential target for acute stage of ischemic stroke therapy.

Keywords: BK channels; ERK; ischemic stroke; microglia; phagocytosis.