Effects of In Vivo Intracellular ATP Modulation on Neocortical Extracellular Potassium Concentration

Abstract

Neuronal and glial activity are dependent on the efflux of potassium ions into the extracellular space. Efflux of K is partly energy-dependent as the activity of pumps and channels which are involved in K transportation is ATP-dependent. In this study, we investigated the effect of decreased intracellular ATP concentration ([ATP]i) on the extracellular potassium ion concentration ([K]o). Using in vivo electrophysiological techniques, we measured neocortical [K]o and the local field potential (LFP) while [ATP]i was reduced through various pharmacological interventions. We observed that reducing [ATP]i led to raised [K]o and DC-shifts resembling spreading depolarization-like events. We proposed that most likely, the increased [K]o is mainly due to the impairment of the Na/K ATPase pump and the ATP-sensitive potassium channel in the absence of sufficient ATP, because Na/K ATPase inhibition led to increased [K]o and ATP-sensitive potassium channel impairment resulted in decreased [K]o. Therefore, an important consequence of decreased [ATP]i is an increased [K]o. The results of this study acknowledge one of the mechanisms involved in [K]o dynamics.

Two decades of astrocytes in neurovascular coupling

“…Ex vivo models of cerebral ischemia based on the application of hypoxic conditions revealed rapid depolarization of neuronal and glial cells resulting from changes in the extracellular ion concentration and resembling spreading depression ( Müller and Somjen, 2000 ). In the ischemic core, acute ATP depletion indeed impairs the activity of Na + /K + -ATPase and opens ATP-sensitive potassium channels, resulting in substantial [K + ] o increase ( Dreier and Reiffurth, 2015 ; EbrahimAmini et al, 2022 ). While a moderate elevation of extracellular K + is a powerful vasodilatory signal due to its hyperpolarizing effect, [K + ] o exceeding 20 mM can result in a diffuse constriction of local vasculature by direct depolarization of mural cells ( Filosa et al, 2006 ).…”