SUMOylation of Na_V1.2 channels mediates the early response to acute hypoxia in central neurons.

ABSTRACT: The mechanism for the earliest response of central neurons to hypoxia-an increase in voltage-gated sodium current (I_Na)-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 Na_V1.2 channels increases I_Na. The time-course for SUMOylation of single Na_V1.2 channels at the cell surface and changes in I_Na coincide, and both are prevented by mutation of Na_V1.2-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 th

SUBMITTER: Plant LD 

PROVIDER: S-EPMC5283832 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature