Bidirectional astrocytic GLUT1 activation by elevated extracellular K+

The acute rise in interstitial K+ that accompanies neural activity couples the energy demand of neurons to the metabolism of astrocytes. The effects of elevated K+ on astrocytes include activation of aerobic glycolysis, inhibition of mitochondrial respiration and the release of lactate. Using a genetically encoded FRET glucose sensor and a novel protocol based on 3-O-methylglucose trans-acceleration and numerical simulation of glucose dynamics, we report that extracellular K+ is also a potent and reversible modulator of the astrocytic glucose transporter GLUT1. In cultured mouse astrocytes, the stimulatory effect developed within seconds, engaged both the influx and efflux modes of the transporter, and was detected even at 1 mM incremental K+. The modulation of GLUT1 explains how astrocytes are able to maintain their glucose pool in the face of strong glycolysis stimulation. We propose that the stimulation of GLUT1 by K+ supports the production of lactate by astrocytes and the timely delivery of glucose to active neurons.

Automated summary

The acute rise in interstitial K+ levels during neural activity connects the energy demands of neurons with the metabolism of astrocytes. Elevated K+ levels stimulate aerobic glycolysis, inhibit mitochondrial respiration, and promote the release of lactate in astrocytes. The modulation of the glucose transporter GLUT1 by K+ allows astrocytes to maintain their glucose pool, support lactate production, and deliver glucose to active neurons.