Following fusion, synaptic vesicles do not always release all of their neurotransmitter. According to one model, neurotransmitters bind to a charged matrix within secretory vesicles, and release requires entry of counterions. In the current issue of Neuron, Krapivinsky et al. demonstrate that TRPM7 is localized to synaptic vesicles and is required for release of the positively charged neurotransmitter acetylcholine. The results raise the possibility that TRPM7 is the enigmatic channel that supplies counterions for neurotransmitter release.