KCNQ5 channels control resting properties and release probability of a synapse

Little is known about which ion channels determine the resting electrical properties of presynaptic membranes. In recordings made from the rat calyx of Held, a giant mammalian terminal, we found that resting potential is controlled by KCNQ (Kv7) K(+) channels, most likely KCNQ5 (Kv7.5) homomers. Unlike most KCNQ channels which activate only upon depolarizing stimuli, the presynaptic channels began to activate just negative to rest. As a result, blockers and activators of KCNQ5 depolarized or hyperpolarized nerve terminals, respectively, markedly altering resting conductance. Moreover, the background conductance set by KCNQ5 channels, in concert with Na(+) and HCN channels, determined the size and timecourse of the response to subthreshold stimuli. Signaling pathways known to directly affect exocytic machinery also regulated KCNQ5 channels, and increase or decrease of KCNQ5 channel activity controlled release probability through alterations in resting potential. Thus, ion channel determinants of presynaptic resting potential also control synaptic strength.