Fig. 7

Molecular dissection of processes underlying spatiotemporal IOS and VSD generation. a: Neuronal and glial proteins underlying VSD mechanism. First, stimulus of the Schaffer collaterals depolarizes neurons via Glu receptor activation. The released Glu almost instantly activates glial EAAT2, therefore the first 5 ms of the VSD signal represents both neuronal and glial depolarization. Neuronal depolarization leads to additional Glu release and the elevation of extracellular [K⁺] and alteration of extracellular [Cl⁻]. The elevated extracellular [K⁺] activates glial K_ir4.1 channel and Na⁺/K⁺ ATPase which are responsible for the late VSD response. The altered extracellular [Cl⁻] leads to the activation of non-specific anion channels and transporters which also contribute to the VSD signal. b: Neuronal and glial proteins underlying IOS mechanism. First, neurons in the pyramidal layer are activated by Schaffer collateral stimulation leading to swelling of their soma, followed by swelling of glial cells in the dendritic region. Glial activity related IOS appears as the consequence of neuronal activation. Neurons induce glial IOS through altered extracellular [K⁺] and [Cl⁻] concentration by depolarization, by their KCC2 cotransporter and by the release of glutamate. IOS is mediated on glial cells via the EAAT2, anion channels and transporters, K_ir4.1 channel and Na⁺/K⁺ ATPase. Proteins underlying VSD or IOS mechanism are sized in accordance with their contribution to IOS and VSD genesis