The Decrease in the Presynaptic Calcium Current Is a Major Cause of Short-Term Depression at a Calyx-Type Synapse

Repetitive nerve firings cause short-term depression (STD) of release at many synapses. Its underlying mechanism is largely attributed to depletion of a readily releasable vesicle pool (RRP) and a decreased probability of releasing a readily releasable vesicle during an action potential. Which of these two mechanisms is dominant and the mechanism that decreases the release probability remain debated. Here, we report that a decreased release probability is caused by a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q-type channels at the calyx of Held in rat brainstem. This mechanism was the dominant cause of STD in a wide range of stimulation conditions, such as during 2 to 20 action potential-equivalent stimuli (AP-e) at 0.2–30 Hz and after 2 to 20 AP-e at 0.2–100 Hz. Only during ≥100 Hz AP-e was depletion the dominant mechanism.