Biophysical Society Conference | Tahoe 2023

Proton Reactions: From Basic Science to Biomedical Applications

Tuesday Speaker Abstracts

ACTIVITIES OF VOLTAGE-GATED PROTON CHANNELS ON INTRACELLULAR MEMBRANES Takafumi Kawai 1 ; Yoshifumi Okochi 1 ; Yasushi Okamura 1 ; 1 Graduate School of Medicine, Osaka University, Dept. Physiology, Suita, Japan Voltage-gated proton channel plays critical roles in sustained enzyme activity for reactive oxygen species production in activated immune cells by canceling charge imbalance and intracellular acidification that result from activity of NADPH oxidase. In fact, granulocytes from HVCN1-gene knockout mice (which encodes Hv1/VSOP protein) showed reduced production of ROS upon stimulation than in wild type mice. Less remarkable neuronal cell damage was induced upon brain ischemia in HVCN1 deficient mice than in wild-type mice (1, 2). However, paradoxically, we reported that ROS production level in cultured microglia of HVCN1 deficient mice was higher than that of wild type mice and that protein carbonylation of the brain of HVCN1 deficient mice was enhanced than that of the wild type mice (2). We also reported that aged animal of HVCN1 deficient mice showed enhanced pattern of behavior in open-field test which is known to be related to anxiety (3). Enhanced ROS production was also suggested in Kupffer cells from HVCN1 deficient mice which showed higher production of glucose from hepatocyte than in wild type mice (4). To gain insights into molecular mechanisms of function of Hv1 in vivo, we have recently generated a mouse strain which expresses Hv1-GFP fusion protein under the CAG promoter. Cultured microglia from this strain showed presence of Hv1 in intracellular membranes besides plasma membrane. In this talk, we will present our recent studies on functions of Hv1 on intracellular membranes. [references]1. Wu LJ, et al. (2012) The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. Nature Neurosci. 15(4):565-73.2. Kawai T, et al. (2017) Unconventional role of voltage-gated proton channels (VSOP/Hv1) in regulation of microglial ROS production. J. Neurochem. 142(5), 686 6993. Kawai T, et al. (2020) Regulation of hepatic oxidative stress by voltage-gated proton channels (Hv1/VSOP) in Kupffer cells and its potential relationship with glucose metabolism. FASEB J.34(12):15805-15821.4. Kawai T, et al. (2021) Heterogeneity of microglial proton channel in different brain regions and its relationship with aging. J eurochem. 157(3):624 641.

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