Fig. 3. Lowering [Ca²⁺]_o alters neuronal activity.

(A) Schematic diagram of a neural circuit characterized by an activity-dependent local decrease in [Ca²⁺]_o. (B) Lowering [Ca²⁺]_o can reduce the strength of synaptic signaling. As [Ca²⁺]_o falls, the reduced driving force for Ca²⁺ influx through voltage-gated Ca²⁺ channels (Ca_v) leads to weakened presynaptic glutamate release, and, in extreme cases, action potential failure. Green arrow directions and widths reflect the direction and strength of the driving force for primarily Na⁺ influx; excitatory postsynaptic potential (EPSP) amplitudes are shown by schematic membrane potential traces. (C) The effective membrane potential across voltage-gated channels is partly governed by the high concentration of negatively charged residues on these channels’ interstitial domains. Under conditions of physiological [Ca²⁺]_o (1.2 mM, left) the negatively-charged residues are largely neutralized by divalent cations (both Ca²⁺ and Mg²⁺). As a result, the local effective membrane potential is similar to the soma. Conversely, lowering the [Ca²⁺]_o to, for example 0.6 mM as occurs during seizures, exposes the negative on the channels’ interstitial domains resulting in a local depolarizing the membrane and increasing neuronal activity through voltage-gated channels.