Chelation of synaptic zinc induces overexcitation in the hilar mossy cells of the rat hippocampus

Subunit-Dependent High-Affinity Zinc Inhibition of Acid-Sensing Ion Channels

“…Consistent with an inhibitory role of synaptically released Zn 2ϩ in neuronal excitation, Cole and colleagues (2000) have demonstrated that Zn 2ϩ transporter 3 knock-out mice, which lack histochemically reactive Zn 2ϩ in synaptic vesicles, were much more susceptible to kainic acid-induced limbic seizures than wild-type mice. Similarly, studies by Blasco-Ibanez et al (2004) demonstrated that chelation of synaptic zinc induced overexcitations of hilar mossy cells in rat hippocampus. In pathological conditions such as brain ischemia during which severe acidosis occurs, a moderate increase of Zn 2ϩ in the extracellular space may serve as a neuroprotective measure through its inhibition of ASICs and NMDA channels.…”

Effect of ZnCl2and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

“…[26][27][28][29] When DEDTC was applied to the bovine retina, the b-wave amplitude starts to decrease within 15-20 min of superfusion ( Figure 5A). The initial b-wave amplitude was 54.8 ± 0.8 µV (n = 5), and decreased significantly (p < 0.01) to 42.7 ± 1.3 µV (n = 3) by adding DEDTC (30 µM), and consecutively to 31.2 ± 2.0 µV (n = 5) by adding 100 µM DEDTC.…”

Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures

“…Synaptically-released Zn 2+ has been suggested to regulate neuronal excitability and modulate the severity of seizure activity (Vogt et al 2000; Smart et al 2004; Sensi et al 2009). Indeed, genetic removal of synaptic Zn 2+ via ZnT3 deletion leads to enhanced susceptibility to epileptic seizures (Cole et al 1999; Cole et al 2000), and importantly, deficiencies in plasma Zn 2+ levels have been associated with human epileptic disorders (Goldberg et al 1982; Blasco-Ibanez et al 2004; Ganesh et al 2008; Farahani et al 2013; Seven et al 2013; Wojciak et al 2013; Saad et al 2014). Moreover, studies in kindling models of epilepsy suggest that seizure activity can be moderated via Zn 2+ administration (Elsas et al 2009; Baraka et al 2012).…”