Azin EbrahimAmini

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.

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o. We hypothesized that in vivo photostimulation of eNpHR-expressing astrocytes leads to a decreased [K]o. Using optogenetic and electrophysiological techniques we showed that stimulation of eNpHR-expressing astrocytes resulted in a significantly decreased resting [K]o and evoked K responses. The amplitude of the concomitant spreading depolarization-like events also decreased. Our results imply that astrocytic membrane potential modification could be a potential tool for adjusting the [K]o.

Epilepsy afflicts up to 1.6% of the population and the mechanisms underlying the appearance of seizures are still not understood. In past years, many efforts have been spent trying to understand the mechanisms underlying the excessive and synchronous firing of neurons. Traditionally, attention was pointed towards synaptic (dys)function and extracellular ionic species (dys)regulation. Recently, novel clinical and preclinical studies explored the role of brain metabolism (i.e., glucose utilization) of seizures pathophysiology revealing (in most cases) reduced metabolism in the inter-ictal period and increased metabolism in the seconds preceding and during the appearance of seizures. In the present review, we summarize the clinical and preclinical observations showing metabolic dysregulation during epileptogenesis, seizure initiation, and termination, and in the inter-ictal period. Recent preclinical studies have shown that 2-Deoxyglucose (2-DG, a glycolysis blocker) is a novel therapeutic approach to reduce seizures. Furthermore, we present initial evidence for the effectiveness of 2-DG in arresting 4-Aminopyridine induced neocortical seizures in vivo in the mouse.