The mechanism for the earliest response of central neurons to hypoxia-an increase in voltage-gated sodium current (INa)-has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of NaV1.2 channels increases INa. The time-course for SUMOylation of single NaV1.2 channels at the cell surface and changes in INa coincide, and both are prevented by mutation of NaV1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of INa in hypoxic brain damage, the SUMO pathway and NaV1.2 are identified as potential targets for neuroprotective interventions.
Pharmacology, Toxicology and Pharmaceutical Science
5
16%
Neuroscience
5
16%
Agricultural and Biological Sciences
3
10%
Medicine and Dentistry
3
10%
Other
1
3%
Unknown
8
26%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 February 2020.
All research outputs
#14,304,007
of 22,925,760 outputs
Outputs from eLife
#12,103
of 13,896 outputs
Outputs of similar age
#229,792
of 421,162 outputs
Outputs of similar age from eLife
#306
of 366 outputs
Altmetric has tracked 22,925,760 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,896 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 36.9. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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We're also able to compare this research output to 366 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
