Postsynaptic zinc potentiation elicited by KCl depolarization at hippocampal mossy fiber synapses

Abstract

The hippocampal mossy fibers contain a substantial quantity of loosely-bound zinc in their glutamatergic presynaptic vesicles, which is released in synaptic transmission processes. Despite the large number of studies about this issue, the zinc changes related to short and long-term forms of potentiation are not totally understood. This work focus on zinc signals associated with chemically-induced mossy fiber synaptic plasticity, in particular on postsynaptic zinc signals evoked by KCl depolarization. The signals were detected using the medium affinity fluorescent zinc indicator Newport Green. The application of large concentrations of KCl, 20 mM and 60 mM, in the extracellular medium evoked zinc potentiations that decreased and remained stable after washout of the first and the second media, respectively. These short and long-lasting enhancements are considered to be due to zinc entry into postsynaptic neurons. We have also observed that following established zinc potentiation, another application of 60 mM KCl only elicited further enhancement when combined with external zinc. These facts support the idea that the KCl-evoked presynaptic depolarization causes higher zinc release leading to zinc influx into the postsynaptic region.

FAD-Linked Autofluorescence and Chemically-Evoked Zinc Changes at Hippocampal Mossy Fiber-CA3 Synapses

“…These changes have a lower amplitude and a slower time course than those of the similarly evoked fluorescence signals observed in slices incubated with the zinc indicator Newport Green. The latter signals, corresponding to the total fluorescence changes in this work, have previously been described by Bastos et al [22]. The application of 20 mM KCl promotes the depolarization of the presynaptic membrane, mediated by voltage dependent channels (VDKCs), to a resting value of about −54 mV [13].…”

“…The experiments were performed in the synaptic system mossy fibers-CA3 pyramidal cells, using the brain of pregnant Wistar rat females (16-18 weeks old), kindly provided by the CNC (Center for Neurosciences) laboratory (as stated in the acknowledgments). The hippocampal slices were prepared as previously described [22,24]. Briefly, after cervical dislocation, the isolated brain was rapidly cooled (5-8°C) in oxygenated (95% O 2 , 5% CO 2 ) artificial cerebrospinal fluid (ACSF), containing (in mM): NaCl 124; KCl 3.5; NaHCO 3 24; NaH 2 PO 4 1.25; MgCl 2 2; CaCl 2 2 and D-glucose 10, pH 7.4.…”

“…In previous studies, performed using intracellularly trapped fluorescent dyes as zinc probes, it has been shown that single and tetanic stimulation of mossy fibers evoke zinc release and postsynaptic intracellular zinc rises [17][18][19]. It has also been reported that the application of high external potassium concentrations elicits a strong depolarization in the cells [20,21], as well as postsynaptic zinc enhancements [22]. However, the application of intense tetanic stimulation caused a depression of zinc and glutamate release, which was reduced by the application of the K ATP channel blocker tolbutamide [14].…”

General Aspects of Metal Ions as Signaling Agents in Health and Disease

“…The release of zinc and its interaction with the receptors of the postsynaptic membrane plays a significant role in long-term potentiation (LTP) and thus contributes to synaptic plasticity, which has been largely studied using animal models [ 104 , 107 , 108 , 109 ]. Simultaneously, studies in rats have shown that chelatable zinc ion homeostasis, and their proportion outside and inside neurons, is disturbed during acute behavioral stress.…”

“…Nevertheless, there is experimental confirmation that zinc ions can be successfully released into the synaptic cleft as a result of electrical stimulation, for example [ 114 ]. Additionally, in some cases, enhancement of Zn 2+ -dependent potentiation is observed on the postsynaptic side, and may be regulated by changes in the concentration of other cations like K + [ 108 ].…”