There is much debate as to whether SV fusion in nerve terminals can occur via a “kiss-and-run” (KR) mode of exocytosis and this has been studied, herein, using cerebrocortical synaptosomes from adult male Wistar rats. The synaptosomes were stimulated with 30 mM K+ (HK) and 5 mM [Ca2+]o allowing them to be maximally loaded with FM2-10 styryl dye and were then studied for exocytosis of the dye. Maximal FM2-10 dye release occurs only when SVs fuse via Full Fusion (FF) whereas glutamate (Glu; the major neurotransmitter present) can be fully released by both, KR and FF. In this study, various secretagogues [HK, 1 mM 4-aminopyridine (4AP) and 5 μM ionomycin (ION)] in the presence of 5 mM [Ca2+]o were used to stimulate a single round of SV exocytosis from both the readily releasable pool (RRP) and reserve/recycling pool (RP) of SVs, and FM2-10 dye and Glu release measured. We found that inhibition of dynamins by dynasore (160 μM) causes more dye to be released with 4AP (p<0.05) and ION (p<0.05) stimulation but there was no extra dye release when HK was employed. On the other hand, inhibition of myosin-II by blebbistatin (50 μM) increased the dye release induced by HK stimulation (p<0.05) but had no effect on 4AP or ION evoked release. Neither dynasore nor blebbistatin had an effect on Glu release evoked by any of the stimuli. This indicates that dynamins or myosin-II can be responsible for the closure of the SV pore during KR depending upon the level of [Ca2+]i that the exocytosing vesicles are exposed to. The results suggest that dynamins are functional at active zones only at lower [Ca2+]i that can be produced by 4AP or ION stimulation whilst myosin-II is only activated at higher [Ca2+]i at the active zone that can be produced by HK stimulation. In order to investigate further such Ca2+ dependencies, synaptosomes prepared from streptozotocin-treated rats – a model of type 1 diabetes – were used as these exhibited both a larger amount of KR release (due to some RP undergoing KR fusion) and a larger change in [Ca2+]i upon stimulation. Interestingly, it was found that myosin-II was responsible for the KR during 4AP stimulation (due presumably to higher [Ca2+]i being achieved at the active zones). In such diabetic rats, myosin-II were responsible for the KR of the RRP during HK stimulation but dynamins were responsible for the regulation of the mode of exocytosis of the RP as such vesicles never get exposed to the high [Ca2+]i required for the activation of myosin-II. This idea of Ca2+ dependent regulation of the two proteins is being further investigated by regulating the [Ca2+]i by other means. Furthermore, The specific role of dynamin I or dynamin II in the closure of the fusion pore is currently being studied.