Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca²⁺ acting across two Ca²⁺ nanodomains, one between plasma membrane P/Q-type Ca²⁺ channels and endoplasmic reticulum (ER) ryanodine receptors, and another between ryanodine receptors and large conductance, voltage- and Ca²⁺-activated K⁺ (BK) channels. Each spike triggered Ca²⁺-induced Ca²⁺ release from the ER immediately beneath somatic, but not axonal or dendritic, plasma membrane. Moreover, immunolabeling demonstrated close apposition of ryanodine receptors and BK channels. Double-nanodomain coupling between somatic plasma membrane and hypolemmal ER cisterns provides a unique mechanism for rapid control of action potentials on the millisecond timescale.