Fig. 2. Changes in [K⁺]_o alters neuronal activity.

(A) Increases in [K⁺]_o from resting levels (left), as seen in wakefulness and locomotion (middle) or pathological states (right), depolarize the neuronal membrane potential closer to the activation threshold of voltage-gated Na⁺ channels (Na_v) in part through a decrease in outward-directed K⁺ currents and increases in regulatory inward-rectifying K⁺ currents (middle). (B) When [K⁺]_o is increased from 3.5 to 5 mM (middle) the depolarized membrane potential may enable increased activation of voltage-gated Ca²⁺ channels (Ca_v), triggering higher levels of released glutamate. If [K⁺]_o increases further, up to a level of roughly 9 mM, this depolarizes the membrane potential at a level that does not allow the Na_v channels to reach their closed state, but rather locks them in their inactive state, leading to gradually fewer action potentials being fired, and as a result lower levels of glutamate being released.