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 (t(1/2)) of 12 +/- 2 and 32 +/- 4 s, respectively. Aquaporin-4 (AQP4) deletion slowed K(+) reuptake about twofold, suggesting AQP4-dependent K(+) uptake by astroglia.