Tandem-pore domain and inwardly rectifying potassium channels: K ⁺ buffering by retinal (Müller) glial cells and cortical astrocytes

Glial cells outnumber neurons in brain about 10 times and are more resistant to ischemia and stroke than the neighboring neurons. For a long time, glial cells were the unacknowledged partners of neurons, "the silent brain", until the recent discovery that (i) de novo neurogenesis is due to glial progenitors giving birth to new neurons, (ii) bidirectional signaling between glia and neurons regulates the neuronal network and (iii) neuronal activation of glia results in changes of blood vessel diameter for better blood circulation and probably potassium buffering. The unique properties and crucial roles of glial cells require a highly hyperpolarized membrane potential (about 20-30 mV below neuronal), which is necessary for transport systems in glia to clear glutamate, GABA, dopamine, potassium, etc., from the extracellular space. Without these transport systems neurons would simply die. If potassium channels and, thus K⁺-clearance, are impaired in glia, epileptiform activity is induced in neurons, accompanied by waves of high extracellular K⁺ (spreading depression) which may reach up to 60 mM [K⁺]_o. This mini-review will emphasize the role of glial specific potassium inwardly rectifying (Kir) channels, Kir4.1 and Kir2.1, and two-pore domain (2P-domain), TASK and TREK type, potassium channels that underlie both the maintenance of membrane potential and the K⁺-buffering mechanisms.