Changes in the speed of endocytosis and the underlying signalling pathways. (A) Schematic representation of the relationship between the speed of endocytosis, the level of intracellular calcium produced by increasing numbers of action potentials, and the signalling pathways activated by intracellular calcium when there is just a single action potential (i), a small burst of action potentials (ii), and a large burst of action potentials (iii). (B) Calcium levels are low when there is just one action potential (i), so calcineurin (CaN) is not activated, allowing Cdk5 to maintain high levels of phosphorylation of dynamin (P-dynamin). As the number of action potentials increases (ii), there are more calcium ions to activate the calcineurin, which results in a shift towards dephosphorylated dynamin. This can then bind to syndapin, and this interaction increases the rate of endocytosis. However, as the number of action potentials, and hence calcium levels, increase further (iii), a second calcium-dependent pathway with unknown molecular components is activated, and this reduces the rate of endocytosis.