Bidirectional and reciprocal control of astrocyte free calcium by modest fluctuations in external potassium

Abstract

Astrocytes sense and respond to changes in the concentration of extracellular K+, and separately contribute to multiple physiological processes through Ca2+ dependent mechanisms. Yet, whether a modest change in [K+]o impacts astrocyte free Ca2+ remains unclear. Using relative or quantitative two-photon fluorescence Ca2+ imaging in acute brain slices or in vivo in the somatosensory cortex from Sprague Dawley rats and C57Bl/6 mice, we showed that changes to external K+ (+/-1mM to 2.5mM) reciprocally controls the astrocyte Rhod-2 or OGB-1 Ca2+-dependent fluorescence in the soma, major processes and endfeet. The astrocyte Ca2+ decrease when [K+]o was elevated was sensitive to lowering the external concentration of Ca2+, Cl-, and HCO3-, but not Na+. Unexpectedly, the phenomenon was blocked by inhibiting K-Cl cotransport. Picrotoxin induced ictal neural activity drove an analogous decrease of astrocyte Ca2+. K+ mediated cerebral arteriole dilation in brain slices was also sensitive to inhibiting K-Cl cotransport as well as whole-cell patching a peri-arteriole astrocyte which perturbs normal Ca2+, Cl- and HCO3- concentration gradients. These data reveal subtle, bidirectional regulation of astrocyte free Ca2 via fluctuations of [K+]o within the physiological range.