Effect of ZnCl<sub>2</sub>and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

Siapich, Siarhei A.; Wrubel, H.; Albanna, Walid; Alnawaiseh, Maged; Hescheler, Jürgen; Weiergräber, Marco; Lüke, Matthias; Schneider, Toni

doi:10.3109/02713680903509410

Cited by 18 publications

(26 citation statements)

References 41 publications

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“…Ni 2+ ‐sensitive retinal signalling can be recorded as the increase in the ERG b‐wave amplitude after superfusion of low (15 μ m ) NiCl 2 solutions. For the bovine retina, a similar amplitude increase was observed when superfusing ZnCl 2 (Siapich et al. 2010), which represents the more physiological cation.…”

Section: Discussionsupporting

confidence: 56%

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina

Alnawaiseh

Albanna

Chen

et al. 2011

Acta Ophthalmologica

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PurposeLight-evoked responses from vertebrate retinas were recorded as an electroretinogram (ERG). The b-wave is the most prominent component of the ERG, and in the bovine retina its NiCl2-sensitive component was attributed to reciprocal signalling by pharmacoresistant R-type voltage-gated Ca2+ channels, which similar to other voltage-dependent Ca2+ channels trigger and control neurotransmitter release. The murine retina has the great advantage that the effect of gene inactivation for Ni2+-sensitive Ca2+ channels can be analysed to prove or disprove that any of these Ca2+ channels is involved in retinal signalling.MethodsSuperfused retinas from different murine genotypes lacking either one or both highly Ni2+-sensitive voltage-gated Ca2+ channels were used to record their ex vivo ERGs.ResultsThe isolated retinas from mice lacking Cav2.3 R-type or Cav3.2 T-type or both voltage-gated Ca2+ channels were superfused with a NiCl2 (15 μm) containing nutrient solution. The change in the b-wave amplitude and implicit time, caused by NiCl2, was calculated as a difference spectrum and compared to data from control animals. From the results, it can be deduced that Cav2.3 contributes rather to a later component in the b-wave response, while in the absence of Cav3.2 the gain of Ni2+-mediated increase in the b-wave amplitude is significantly increased, probably due to a loss of reciprocal inhibition to photoreceptors. Thus, each of the Ni2+-sensitive Ca2+ channels contributes to specific features of the b-wave response.ConclusionBoth high-affinity Ni2+-sensitive Ca2+ channels contribute to transretinal signalling. Based on the results from the double knockout mice, additional targets for NiCl2 must contribute to transretinal signalling, which will be most important for the structurally similar physiologically more important heavy metal cation Zn2+.

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Section: Discussionsupporting

confidence: 56%

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina

Alnawaiseh

Albanna

Chen

et al. 2011

Acta Ophthalmologica

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“…Splice variants of Ca v 2.3 from different species (see also Table 1, Table 2) as well as auxiliary subunits are tissue-specifically expressed [9]. In addition to expression in neuronal [65,66,67,68,69] and endocrine tissues [70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85], Ca v 2.3 transcripts have also been detected in mamalian heart [86,87,88], kidney [70,86,89], sperm [90,91,92,93], spleen [3], and retina [94,95,96,97]. Furthermore, the subcellular distribution of Ca v 2.3 has been investigated revealing both somatodendritic and presynaptic expression [98] with additional functional specificities [99].…”

Section: The Cav23 Voltage-gated Ca2+ Channelmentioning

confidence: 99%

How “Pharmacoresistant” is Cav2.3, the Major Component of Voltage-Gated R-type Ca2+ Channels?

2013

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Membrane-bound voltage-gated Ca2+ channels (VGCCs) are targets for specific signaling complexes, which regulate important processes like gene expression, neurotransmitter release and neuronal excitability. It is becoming increasingly evident that the so called “resistant” (R-type) VGCC Cav2.3 is critical in several physiologic and pathophysiologic processes in the central nervous system, vascular system and in endocrine systems. However its eponymous attribute of pharmacologic inertness initially made in depth investigation of the channel difficult. Although the identification of SNX-482 as a fairly specific inhibitor of Cav2.3 in the nanomolar range has enabled insights into the channels properties, availability of other pharmacologic modulators of Cav2.3 with different chemical, physical and biological properties are of great importance for future investigations. Therefore the literature was screened systematically for molecules that modulate Cav2.3 VGCCs.

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“…(ii) Sodium diethyldithiocarbamate trihydrate (DEDTC) is a watersoluble organosulfur compound used as a chelating agent for transition metal ions and to remove zinc from human cell cultures (20,21). DEDTC (Sigma-Aldrich, D3506-100G) was diluted to a 0.1 M stock solution in distilled water (dH 2 O).…”

Section: Methodsmentioning

confidence: 99%

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin

Laskaris

Atrouni

Calera

et al. 2016

Antimicrob Agents Chemother

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f Aspergillus fumigatus can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat A. fumigatus infections. In this study, we examined the in vitro effects of seven chelators using a bioluminescent strain of A. fumigatus. 1,10-Phenanthroline and N,N,N=,N=-tetrakis(2-pyridylmethyl) ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth. Intraperitoneal administration of either phenanthroline or TPEN resulted in a significant improvement in survival and decrease of weight loss and fungal burden for immunosuppressed mice intranasally infected with A. fumigatus. In vitro both chelators had an indifferent effect when employed in combination with caspofungin. The use of TPEN in combination with caspofungin also significantly increased survival compared to that when using these drugs individually. Our results suggest that zinc chelation may be a valid strategy for dealing with A. fumigatus infections and that both phenanthroline and TPEN could potentially be used either independently or in combination with caspofungin, indicating that their use in combination with other antifungal treatments might also be applicable.A spergillus fumigatus is a widespread soil-dwelling fungal saprotroph (1). It is one of the most ubiquitous fungal species with airborne conidia, and it is estimated that all humans inhale several hundred conidia each day (2). These are completely innocuous to immunocompetent hosts. However, the conidia are able to develop and cause invasive pulmonary aspergillosis (IPA) in immunocompromised individuals (3). This disease is difficult to treat, with a mortality rate of 45.6% (4). Commonly used drug treatment options include triazoles such as voriconazole, which inhibit ergosterol synthesis, amphotericin B, which binds to ergosterol and thus results in increased permeability of the cell membrane, and echinocandins such as caspofungin, which inhibit glucan synthesis (5).Both fungal and bacterial pathogens require cations to grow within their hosts and utilize specialized mechanisms in order to obtain them (6). Zinc is considered essential for all organisms, including pathogens (7). The average concentration of free Zn 2ϩ in human serum is 0.08 M, which is about 150 times lower than the minimal concentration required for A. fumigatus to grow optimally in a defined liquid medium (8). A. fumigatus possesses three genes, zrfA, zrfB, and zrfC, encoding plasma membrane zinc transporters (8). The zrfA and zrfB genes are required for zinc uptake in acidic Zn-limited environments (7), while zrfC is required for zinc uptake in alkaline environments (9) The zrfC gene is primarily responsible for zinc acquisition within a host's lungs and is required for virulence; zrfA and zrfB contribute to fungal pathogenesis to a lesser extent than zrfC and are not r...

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

Abstract: The stimulatory effect of ZnCl(2) on the ERG b-wave amplitude resembles the stimulatory effect of NiCl(2) and may be mediated rather by the NiCl(2)-sensitive, Ca(v)2.3 E-/R-type voltage-gated Ca(2+) channels than by NiCl(2)-sensitive T-type channels.

Cited by 18 publications

References 41 publications

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina

How “Pharmacoresistant” is Cav2.3, the Major Component of Voltage-Gated R-type Ca2+ Channels?

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin

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

Abstract: The stimulatory effect of ZnCl(2) on the ERG b-wave amplitude resembles the stimulatory effect of NiCl(2) and may be mediated rather by the NiCl(2)-sensitive, Ca(v)2.3 E-/R-type voltage-gated Ca(2+) channels than by NiCl(2)-sensitive T-type channels.

Cited by 18 publications

References 41 publications

Two separate Ni 2+ ‐sensitive voltage‐gated Ca 2+ channels modulate transretinal signalling in the isolated murine retina

Two separate Ni 2+ ‐sensitive voltage‐gated Ca 2+ channels modulate transretinal signalling in the isolated murine retina

How “Pharmacoresistant” is Cav2.3, the Major Component of Voltage-Gated R-type Ca2+ Channels?

Administration of Zinc Chelators Improves Survival of Mice Infected with Aspergillus fumigatus both in Monotherapy and in Combination with Caspofungin

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

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina

Two separate Ni ²⁺ ‐sensitive voltage‐gated Ca ²⁺ channels modulate transretinal signalling in the isolated murine retina