Fusion pores with low conductance are cation selective

Many neurotransmitters are organic ions that carry a net charge, and their release from secretory vesicles is therefore an electrodiffusion process. The selectivity of early exocytotic fusion pores is investigated by combining electrodiffusion theory, measurements of amperometric foot signals from chromaffin cells with anion substitution, and molecular dynamics simulation. The results reveal that very narrow fusion pores are cation selective, but more dilated fusion pores become anion permeable. The transition occurs around a fusion pore conductance of ∼300 pS. The cation selectivity of a narrow fusion pore accelerates the release of positively charged transmitters such as dopamine, noradrenaline, adrenaline, serotonin, and acetylcholine, while glutamate release may require a more dilated fusion pore. [Display omitted] •Exocytotic transmitter release is an electrodiffusion process•Narrow fusion pores are cation selective•Fusion pore ion selectivity decreases as the fusion pore expands For transmission, a fusion pore forms when vesicle and target membranes are brought together by SNARE proteins. Delacruz et al. demonstrate that selectivity of the pore accelerates release of positively charged transmitters such as dopamine, noradrenaline, adrenaline, serotonin, and acetylcholine, while glutamate release may require a more dilated fusion pore.