Tyrosine Phosphorylation Determines Afterdischarge Initiation by Regulating an Ionotropic Cholinergic Receptor

White, Stuart C.; Sturgeon, Raymond M.; Gu, Yueling; Nensi, Alysha; Magoski, Neil S.

doi:10.1016/j.neuroscience.2017.12.049

Cited by 5 publications

(4 citation statements)

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“…Last, ethanol (100% v/v) was used to dissolve N-ethylmaleimide (NEM; 50 mM; E3876, Sigma-Aldrich). The final concentration of DMSO or ethanol in the bath was Յ0.2% (v/v), which in control experiments here or in prior studies was found to have no effect on bag cell neuron holding current, membrane conductance, or membrane potential (Hickey et al, 2010(Hickey et al, , 2013Tam et al, 2011;Sturgeon and Magoski, 2016;White et al, 2018).…”

Section: Methodsmentioning

confidence: 86%

“…Because bath-applying H 2 O 2 alone causes a burst in a minority of clusters, we speculate H 2 O 2 may need to work in concert with ACh, a known input transmitter that gates an ionotropic receptor on bag cell neurons (White and Magoski, 2012;White et al, 2014). Pressure-ejecting ACh onto one side of the cluster depolarizes a neuron recorded on the opposite side; this is because of the transfer of cholinergic current through electrotonic coupling between neurons within the cluster (Kupfermann and Kandel, 1970;Dargaei et al, 2014;White et al, 2018). When H 2 O 2 is bath-applied subsequent to the ACh pressure-ejection, it consistently provokes an afterdischarge-like burst.…”

Section: Discussionmentioning

confidence: 99%

“…We speculated that H 2 O 2 may need to work in concert with the known bag cell neuron input transmitter, ACh (White and Magoski, 2012). Previously, our lab showed that brief pressure-application of ACh to the isolated bag cell neuron cluster would initiate a transient depolarization in a given neuron, sometimes accompanied by afterdischarge-like spiking (White et al, 2018). Thus, in the present study, while again recording from a single bag cell neuron within the cluster, ACh was first pressure-ejected followed by the introduction of H 2 O 2 (Fig.…”

Section: H 2 O 2 Depolarizes Bag Cell Neurons and Initiates An Afterdmentioning

confidence: 99%

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Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Chauhan

Magoski

2019

J. Neurosci.

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Nonselective cation channels promote persistent spiking in many neurons from a diversity of animals. In the hermaphroditic marinesnail, Aplysia californica, synaptic input to the neuroendocrine bag cell neurons triggers various cation channels, causing an ϳ30 min afterdischarge of action potentials and the secretion of egg-laying hormone. During the afterdischarge, protein kinase C is also activated, which in turn elevates hydrogen peroxide (H 2 O 2), likely by stimulating nicotinamide adenine dinucleotide phosphate oxidase. The present study investigated whether H 2 O 2 regulates cation channels to drive the afterdischarge. In single, cultured bag cell neurons, H 2 O 2 elicited a prolonged, concentration-and voltage-dependent inward current, associated with an increase in membrane conductance and a reversal potential of ϳϩ30 mV. Compared with normal saline, the presence of Ca 2ϩ-free, Na ϩ-free, or Na ϩ /Ca 2ϩ-free extracellular saline, lowered the current amplitude and left-shifted the reversal potential, consistent with a nonselective cationic conductance. Preventing H 2 O 2 reduction with the glutathione peroxidase inhibitor, mercaptosuccinate, enhanced the H 2 O 2-induced current, while boosting glutathione production with its precursor, N-acetylcysteine, or adding the reducing agent, dithiothreitol, lessened the response. Moreover, the current generated by the alkylating agent, N-ethylmaleimide, occluded the effect of H 2 O 2. The H 2 O 2-induced current was inhibited by tetrodotoxin as well as the cation channel blockers, 9-phenanthrol and clotrimazole. In current-clamp, H 2 O 2 stimulated burst firing, but this was attenuated or prevented altogether by the channel blockers. Finally, H 2 O 2 evoked an afterdischarge from whole bag cell neuron clusters recorded ex vivo by sharp-electrode. H 2 O 2 may regulate a cation channel to influence long-term changes in activity and ultimately reproduction.

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Section: Methodsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: H 2 O 2 Depolarizes Bag Cell Neurons and Initiates An Afterdmentioning

confidence: 99%

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Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Chauhan

Magoski

2019

J. Neurosci.

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“…We opted to isolate the clusters because our earlier work showed that acetylcholine was more effective in this configuration (White & Magoski 2012; White et al . 2018), likely due to high levels of acetylcholinesterase within the surrounding connective tissue of clusters in the intact ganglion (Giller & Schwartz, 1971). Moreover, this allowed us to assign one cluster from a given animal to the DMSO‐pretreated control group, while the second cluster was placed in an experimental group pretreated for ∼15 min with 5 μM of the pan‐NOX inhibitor 3‐benzyl‐7‐(2‐benzoxazolyl)thio‐1,2,3‐triazolo[4,5‐d]pyrimidine (VAS2870; ten Freyhaus et al .…”

Section: Resultsmentioning

confidence: 99%

Hydrogen peroxide and phosphoinositide metabolites synergistically regulate a cation current to influence neuroendocrine cell bursting

Chauhan-Puri

Lee

Magoski

2021

The Journal of Physiology

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In various neurons, including neuroendocrine cells, non‐selective cation channels elicit plateau potentials and persistent firing. Reproduction in the marine snail Aplysia californica is initiated when the neuroendocrine bag cell neurons undergo an afterdischarge, that is, a prolonged period of enhanced excitability and spiking during which egg‐laying hormone is released into the blood. The afterdischarge is associated with both the production of hydrogen peroxide (H2O2) and activation of phospholipase C (PLC), which hydrolyses phosphatidylinositol‐4,5‐bisphosphate into diacylglycerol (DAG) and inositol trisphosphate (IP3). We previously demonstrated that H2O2 gates a voltage‐dependent cation current and evokes spiking in bag cell neurons. The present study tests if DAG and IP3 impact the H2O2‐induced current and excitability. In whole‐cell voltage‐clamped cultured bag cell neurons, bath‐application of 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), a DAG analogue, enhanced the H2O2‐induced current, which was amplified by the inclusion of IP3 in the pipette. A similar outcome was produced by the PLC activator, N‐(3‐trifluoromethylphenyl)‐2,4,6‐trimethylbenzenesulfonamide. In current‐clamp, OAG or OAG plus IP3, elevated the frequency of H2O2‐induced bursting. PKC is also triggered during the afterdischarge; when PKC was stimulated with phorbol 12‐myristate 13‐acetate, it caused a voltage‐dependent inward current with a reversal potential similar to the H2O2‐induced current. Furthermore, PKC activation followed by H2O2 reduced the onset latency and increased the duration of action potential firing. Finally, inhibiting nicotinamide adenine dinucleotide phosphate oxidase with 3‐benzyl‐7‐(2‐benzoxazolyl)thio‐1,2,3‐triazolo[4,5‐d]pyrimidine diminished evoked bursting in isolated bag cell neuron clusters. These results suggest that reactive oxygen species and phosphoinostide metabolites may synergize and contribute to reproductive behaviour by promoting neuroendocrine cell firing. Key points Aplysia bag cell neurons secrete reproductive hormone during a lengthy burst of action potentials, known as the afterdischarge. During the afterdischarge, phospholipase C (PLC) hydrolyses phosphatidylinositol‐4,5‐bisphosphate into diacylglycerol (DAG) and inositol trisphosphate (IP3). Subsequent activation of protein kinase C (PKC) leads to H2O2 production. H2O2 evokes a voltage‐dependent inward current and action potential firing. Both a DAG analogue, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), and IP3 enhance the H2O2‐induced current, which is mimicked by the PLC activator, N‐(3‐trifluoromethylphenyl)‐2,4,6‐trimethylbenzenesulfonamide. The frequency of H2O2‐evoked afterdischarge‐like bursting is augmented by OAG or OAG plus IP3. Stimulating PKC with phorbol 12‐myristate 13‐acetate shortens the latency and increases the duration of H2O2‐induced bursts. The nicotinamide adenine dinucleotide phosphate oxidase inhibitor, 3‐benzyl‐7‐(2‐benzoxazolyl)thio‐1,2,3‐triazolo[4,5‐d]pyrimidine, attenuates burst firing in bag cell neuron clusters.

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Cholinergic depolarization recruits a persistent Ca²⁺ current in Aplysia bag cell neurons

Lee

Wassef

MacNeil

et al. 2023

Journal of Neurophysiology

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Many behaviors and types of information storage are mediated by lengthy changes in neuronal activity. In bag cell neurons of the hermaphroditic sea snail, Aplysia californica, a transient cholinergic synaptic input triggers an ~30 min afterdischarge. This causes these neuroendocrine cells to release egg laying hormone and elicit reproductive behavior. When acetylcholine is pressure-ejected onto a current-clamped bag cell neuron, the evoked depolarization is far longer than the current evoked by acetylcholine under voltage-clamp, suggesting recruitment of another conductance. Our earlier studies found bag cell neurons to display a voltage-dependent persistent Ca2+ current. Hence, we hypothesized that this current is activated by the acetylcholine-induced depolarization, and sought a selective Ca2+ current blocker. Rapid Ca2+ current evoked by 200-ms depolarizing steps in voltage-clamped, cultured bag cell neurons demonstrated a concentration-dependent sensitivity to Ni2+, Co2+, Zn2+, and verapamil but not Cd2+ or -conotoxin GIVa. Leak subtraction of Ca2+ current evoked by 10-s depolarizing steps using the IC100 of Ni2+, Co2+, Zn2+, or verapamil revealed persistent Ca2+ current, demonstrating persistent current block. Only Co2+ and Zn2+ did not suppress the acetylcholine-induced current, although Zn2+ appeared to impact additional channels. When Co2+ was applied during an acetylcholine-induced depolarization, the amplitude was reduced; furthermore, protein kinase C activation, previously established to enhance the persistent Ca2+ current, extended the depolarization. Therefore, the persistent Ca2+ current sustains the acetylcholine-induced depolarization and may translate brief cholinergic input into afterdischarge initiation. This could be a general mechanism of triggering long-term change in activity using a short-lived input.

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Tyrosine Phosphorylation Determines Afterdischarge Initiation by Regulating an Ionotropic Cholinergic Receptor

Cited by 5 publications

References 84 publications

Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Hydrogen peroxide and phosphoinositide metabolites synergistically regulate a cation current to influence neuroendocrine cell bursting

Cholinergic depolarization recruits a persistent Ca²⁺ current in Aplysia bag cell neurons

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Tyrosine Phosphorylation Determines Afterdischarge Initiation by Regulating an Ionotropic Cholinergic Receptor

Cited by 5 publications

References 84 publications

Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inAplysiaNeuroendocrine Cells

Hydrogen peroxide and phosphoinositide metabolites synergistically regulate a cation current to influence neuroendocrine cell bursting

Cholinergic depolarization recruits a persistent Ca2+ current in Aplysia bag cell neurons

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Cholinergic depolarization recruits a persistent Ca²⁺ current in Aplysia bag cell neurons