K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator

We synthesized a water-soluble, long-wavelength K+ sensor, TAC-Red, consisting of triazacryptand coupled to 3,6-bis(dimethylamino)xanthylium, whose fluorescence increased 14-fold at 0–50 mM K+ with K+-to-Na+ selectivity >30. We visualized K+ waves in TAC-Red–stained brain cortex in mice during spreading depression, with velocity 4.4 ± 0.5 mm/min, and K+ release and reuptake half-times (t1/2) of 12 ± 2 and 32 ± 4 s, respectively. Aquaporin-4 (AQP4) deletion slowed K+ reuptake about twofold, suggesting AQP4-dependent K+ uptake by astroglia.