Inhibition of endocytosis suppresses the nitric oxide-dependent release of Cl- in retinal amacrine cells

摘要: Our lab has previously shown that nitric oxide (NO) can alter the synaptic response properties of amacrine cells by releasing Cl- from internal acidic compartments. This alteration in gradient brings about a positive shift reversal potential GABA-gated current, which convert inhibitory synapses into excitatory synapses. Recently, we have cystic fibrosis transmembrane regulator (CFTR) channel is involved release. Here, test hypothesis (acidic) vesicles are source NO-releasable chick retinal cells. If SVs Cl-, then depleting should decrease oxide-dependent current. The efficacy four inhibitors dynamin (dynasore, Dyngo 4a, Dynole 34–2, and MiTMAB) were evaluated. In order to deplete vesicles, voltage-steps used activate V-gated Ca2+ channels stimulate vesicle cycle either under control conditions or after treatment with inhibitors. Voltage-ramps measure NO-dependent currents both conditions. results reveal activating presence dynasore 4a blocked EGABA. However, also discovered some reduced signaling L-type currents. Conversely, increased neurotransmitter release at autaptic sites. To further resolve mechanism underlying inhibition for currents, tested effects clathrin assembly inhibitor Pitstop 2 found this compound inhibited shift. These data provide evidence multiple on cell transmission. suggest endocytosis disrupts ability NO elicit stores may part be due depletion vesicles.