Voltage-gated calcium channels: Determinants of channel function and modulation by inorganic cations

Neumaier, Felix; Dibué-Adjei, Maxine; Hescheler, Jürgen; Schneider, Toni

doi:10.1016/j.pneurobio.2014.12.003

Cited by 34 publications

(38 citation statements)

References 382 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A-C, addition of 100 μM DEDTC to the extracellular solution containing 10 μM Zn 2+ potently stimulated Ba 2+ inward currents over the whole voltage-range examined without changing the apparent reversal potential. Consistent with a reversal of allosteric suppression by chelation of extracellular Zn 2+ [12,13], DEDTC effects were associated with a significant (p b 0.001) hyperpolarizing shift of the half-maximal activation voltage ( Fig. 3C & D), they were rapid (Fig.…”

Section: Dedtc Zn 2+ Chelation Reverses Tonic Suppression Of Ca V 23supporting

confidence: 67%

“…Besides weakly blocking all voltagegated Ca 2+ channels (VGCCs) [8], Zn 2+ is a potent allosteric antagonist of certain Ca v α 1 subunits (Ca v 2.3 and Ca v 3.2), which possess extracellular metal binding sites with nanomolar to low micromolar Zn 2+ affinity [9][10][11][12][13]. Since Ca v 2.3 VGCCs have been linked to insulin [14][15][16], glucagon [17], and somatostatin (SST) release in mice [18], we compared the effects of Zn 2+ chelation on glucose homeostasis and peptide hormone release in Ca v 2.3-deficient and control mice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Drobinskaya

Neumaier

Pereverzev

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Self Cite

View full text Add to dashboard Cite

Peptide-hormone secretion is partially triggered by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) and gene inactivation of Zn2+-sensitive Cav2.3-type VGCCs is associated with disturbed glucose homeostasis in mice. Zn2+ has been implicated in pancreatic islet cell crosstalk and recent findings indicate that sudden cessation of Zn2+ supply during hypoglycemia triggers glucagon secretion in rodents. Here we show that diethyldithiocarbamate (DEDTC), a chelating agent for Zn2+ and other group IIB metal ions, differentially affects blood glucose and serum peptide hormone level in wild-type mice and mice lacking the Cav2.3-subunit. Fasting glucose and glucagon level were significantly higher in Cav2.3-deficient compared to wild-type mice, while DEDTC Zn2+-chelation produced a significant and correlated increase of blood glucose and serum glucagon concentration in wild-type but not Cav2.3-deficient mice. Glucose tolerance tests revealed severe glucose intolerance in Zn2+-depleted Cav2.3-deficient but not vehicle-treated Cav2.3-deficient or Zn2+-depleted wildtype mice. Collectively, these findings indicate that Cav2.3 channels are critically involved in the Zn2+-mediated suppression of glucagon secretion during hyperglycemia. Especially under conditions of Zn2+ deficiency, ablation or dysfunction of Cav2.3 channels may lead to severe disturbances in glucose homeostasis.

show abstract

Section: Dedtc Zn 2+ Chelation Reverses Tonic Suppression Of Ca V 23supporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Drobinskaya

Neumaier

Pereverzev

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Though TTX blocked the glutamate response to whisker stimulation in FHM2 mice, it had no discernable influence on spontaneous plume frequency in the same animals . To test whether plumes represented action potential-independent but voltage-gated Ca 2+ (Ca V ) channeldependent synaptic vesicular release, we inhibited Ca V channels with Ni 2+ (Neumaier et al, 2015;Zamponi et al, 1996), and observed a halving of spontaneous plume frequency compared to baseline in awake FHM2 mice ( Figure 3D). Spontaneous plumes did not depend on Ca 2+ influx through local presynaptic NMDA receptors (Banerjee et al, 2016;Zhou et al, 2013), as DL-APV did not affect the frequency of plumes in awake FHM2 mice ( Figure S3C).…”

Section: Glutamatergic Plumes Depend On Ca V Mediated Vesicular Releamentioning

confidence: 99%

Non-canonical glutamate signaling in a genetic model of migraine with aura

Parker

Suryavanshi

Melone

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Anomalous mole fraction effect (AMFE) was found in many different types of ion channels such as the voltage gated Ca 2+ -channel [40], the ryanodine receptor [41] or the cyclic nucleotide-gated channel [42] and also the CaCC expressed in Xenopus oocyte [29]. Moreover, studies on mouse and Xenopus tropicalis TMEM16A showed a significant deviation of reversal potential values recorded with different mixtures of Cl − and other anions from the prediction obtained with the Goldman-Hodgkin-Katz equation [28,43].…”

Section: Discussionmentioning

confidence: 99%

Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels

Pifferi

2017

PLoS ONE

View full text Add to dashboard Cite

TMEM16A and TMEM16B encode for Ca2+-activated Cl− channels (CaCC) and are expressed in many cell types and play a relevant role in many physiological processes. Here, I performed a site-directed mutagenesis study to understand the molecular mechanisms of ion permeation of TMEM16B. I mutated two positive charged residues R573 and K540, respectively located at the entrance and inside the putative channel pore and I measured the properties of wild-type and mutant TMEM16B channels expressed in HEK-293 cells using whole-cell and excised inside-out patch clamp experiments. I found evidence that R573 and K540 control the ion permeability of TMEM16B depending both on which side of the membrane the ion substitution occurs and on the level of channel activation. Moreover, these residues contribute to control blockage or activation by permeant anions. Finally, R573 mutation abolishes the anomalous mole fraction effect observed in the presence of a permeable anion and it alters the apparent Ca2+-sensitivity of the channel. These findings indicate that residues facing the putative channel pore are responsible both for controlling the ion selectivity and the gating of the channel, providing an initial understanding of molecular mechanism of ion permeation in TMEM16B.

show abstract

Voltage-gated calcium channels: Determinants of channel function and modulation by inorganic cations

Cited by 34 publications

References 382 publications

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Non-canonical glutamate signaling in a genetic model of migraine with aura

Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels

Contact Info

Product

Resources

About