RT Journal Article SR Electronic T1 Dynamin-1 restrains vesicular release to a sub-quantal mode in mammalian adrenal chromaffin cells JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1255-18 DO 10.1523/JNEUROSCI.1255-18.2018 A1 Qihui Wu A1 Quanfeng Zhang A1 Bin Liu A1 Yinglin Li A1 Xi Wu A1 Shuting Kuo A1 Lianghong Zheng A1 Changhe Wang A1 Feipeng Zhu A1 Zhuan Zhou YR 2018 UL http://www.jneurosci.org/content/early/2018/10/29/JNEUROSCI.1255-18.2018.abstract AB Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca2+-dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and sub-quantal in adrenal chromaffin cells (ACCs), but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report 1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; 2) the KO-increase QS was rescued by dyn1 (but not its deficient mutant or dyn2); 3) the ratio of quantal versus subquantal events was increased by KO; 4) following a release event, more protein contents were retained in WT vs KO vesicles; and 5) the fusion pore size dp was increased from ≤9 to ≥9 nm by KO. Thus, Ca2+-induced exocytosis is generally a sub-quantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells.SIGNIFICANCE STATEMENTCa2+-dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission including synaptic/neuroendocrine forms. To address Ca2+-dependent vesicular neurotransmitter release is “all-or-none” (quantal), we provide compelling evidence that most Ca2+-induced secretory events occur via the sub-quantal mode in native adrenal chromaffin cells. This sub-quantal release mode is promoted by dynamin 1, which is universally required for most secretory cells including neurons and neuroendocrine cells. The present work with genetic mice further confirms that Ca2+-dependent transmitter release is mainly via sub-quantal mode, implicating that sub-quantal release could be also important in other types of cells.