Functions and Mechanisms of the Voltage-Gated Proton Channel Hv1 in Brain and Spinal Cord Injury.

Junyun He,Junfang Wu,Rodney M. Ritzel

doi:10.3389/fncel.2021.662971

Junyun He, Junfang Wu + Show 1 more

Open Access

https://doi.org/10.3389/fncel.2021.662971

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Abstract

The voltage-gated proton channel Hv1 is a newly discovered ion channel that is highly conserved among species. It is known that Hv1 is not only expressed in peripheral immune cells but also one of the major ion channels expressed in tissue-resident microglia of the central nervous systems (CNS). One key role for Hv1 is its interaction with NADPH oxidase 2 (NOX2) to regulate reactive oxygen species (ROS) and cytosolic pH. Emerging data suggest that excessive ROS production increases and requires proton currents through Hv1 in the injured CNS, and manipulations that ablate Hv1 expression or induce loss of function may provide neuroprotection in CNS injury models including stroke, traumatic brain injury, and spinal cord injury. Recent data demonstrating microglial Hv1-mediated signaling in the pathophysiology of the CNS injury further supports the idea that Hv1 channel may function as a key mechanism in posttraumatic neuroinflammation and neurodegeneration. In this review, we summarize the main findings of Hv1, including its expression pattern, cellular mechanism, role in aging, and animal models of CNS injury and disease pathology. We also discuss the potential of Hv1 as a therapeutic target for CNS injury.

Highlights

The central nervous system (CNS) injuries or diseases such as stroke, traumatic brain injury (TBI), spinal cord injury (SCI), and multiple sclerosis (MS), are the leading causes of death and disability in the United States and around the world
To facilitate the development of clinically useful Hv1-active drugs, this review summarizes the current research on the function and mechanisms of the Hv1 channel in CNS injury models including various ischemic and traumatic brain injuries, neurodegenerative disease, and spinal cord injury
We demonstrated that TBI causes intracellular and extracellular acidosis that persist for weeks after injury

Summary

Introduction

The central nervous system (CNS) injuries or diseases such as stroke, traumatic brain injury (TBI), spinal cord injury (SCI), and multiple sclerosis (MS), are the leading causes of death and disability in the United States and around the world. To facilitate the development of clinically useful Hv1-active drugs, this review summarizes the current research on the function and mechanisms of the Hv1 channel in CNS injury models including various ischemic and traumatic brain injuries, neurodegenerative disease, and spinal cord injury.

Results

Conclusion