G-proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage-dependent regulation of mammalian Cav2.1 and Cav2.2 channels

Huang, Xuan; Senatore, Adriano; Dawson, Taylor F.; Quan, Quyen; Spafford, J. David

doi:10.1242/jeb.042242

Cited by 21 publications

(29 citation statements)

References 28 publications

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“…Such inhibition is physiologically distinct in that strong depolarization of the neuron as with bursting would also relieve this inhibition (Brody et al 1997). Expression of another molluskan Ca V 2 channel, the Lymnaea Ca V 2 in HEK293 cells, provides evidence that invertebrate Ca V 2 channels do not show voltagedependent inhibition (Huang et al 2010). Even with vertebrate Ca V 2 channels, voltage-dependent inhibition only accounts for a portion of the G protein-mediated inhibition of the channel.…”

Section: Discussionmentioning

confidence: 99%

“…Heterotrimeric G-protein ␤␥-subunits are known to inhibit Ca V 2 channels through direct interaction with the pore-forming ␣-subunit (Tedford and Zamponi 2006;Zamponi and Currie). This type of inhibition is referred to as voltage-dependent inhibition as it can be relieved with a strong depolarizing prepulse; however, this type of modulation has only been observed with vertebrate Ca V 2 channels (Huang et al 2010). Following isolation of the inward barium current in Aplysia sensory neurons, a strong prepulse to ϩ120 mV, 10 ms before a test pulse to ϩ10 mV was delivered to assess the amount of voltage-dependent inhibition (Fig.…”

Section: Inhibition Of the Isolated Inward Barium Current With Dopamimentioning

confidence: 99%

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Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin

Dunn

Sossin

2013

Journal of Neurophysiology

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Dunn TW, Sossin WS. Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin. J Neurophysiol 110: 2071-2081, 2013. First published August 7, 2013 doi:10.1152/jn.00217.2013.-The inhibition of Aplysia pleural mechanosensory neuron synapses by dopamine and serotonin through activation of endogenous dopaminergic and expressed 5-HT 1Apl(a)/b receptors, respectively, involves a reduction in action potential-associated calcium influx. We show that the inhibition of synaptic efficacy is downstream of the readily releasable pool, suggesting that inhibition is at the level of calcium secretion coupling, likely a result of the changes in the calcium current. Indeed, the inhibitory responses directly reduce a Ca V 2-like calcium current in isolated sensory neurons. The inhibition of the calcium current is voltage independent as it is not affected by a strong depolarizing prepulse, consistent with other invertebrate Ca V 2 calcium currents. Similar to voltage-independent inhibition of vertebrate nociceptors, inhibition was blocked with Src tyrosine kinase inhibitors. The data suggest a conserved mechanism by which G protein-coupled receptor activation can inhibit the Ca V 2 calcium current in nociceptive neurons.Aplysia; calcium current; dopamine; nocioceptor; voltage-dependent inhibition THE PLEURAL SENSORY NEURONS of the marine mollusk Aplysia californica function as body wall mechanosensory neurons with a nociceptive role (Walters et al. 1983a(Walters et al. ,b, 2004. Stimulation of the pleural sensory neurons excite defensive withdrawal motorneurons resulting in defensive behaviors (Walters et al. 1983a). Modulatory substances such as FMRFamide and dopamine reduce pleural sensory neuron excitability and synaptic efficacy to withdrawal motorneurons (Dunn et al. 2012;Edmonds et al. 1990;Guan et al. 2003). Such inhibition of pleural sensory neuron activity would serve an analgesic or hypoalgesic role, reducing the sensation of stimuli to the body wall and foot of the animal.Previously we reported that dopamine had a strong inhibitory effect on synaptic efficacy at synapses between Aplysia pleural mechanosensory neurons and defensive withdrawal motor neurons in culture (Dunn et al. 2012). The inhibitory response also included a large reduction in the presynaptic calcium flux. However, it was not determined whether the reduction in the action potential-associated calcium transient was through direct inhibition of the Ca V 2-like calcium current, the current responsible for triggering transmitter release, as was suggested previously for FMRFamide (Edmonds et al. 1990). Alternatively, the reduction in the calcium transient may be indirect, through changes in potassium currents that affect action potential duration, or from failure of the action potential to propagate to and depolarize all the presynaptic terminals.Here we further examine the mechanisms of dopaminergic inhibition of synaptic efficacy at Aplysia sensory to motor neuron pairs in culture. We show that the action potential does conduct ...

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Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of the Isolated Inward Barium Current With Dopamimentioning

confidence: 99%

Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin

Dunn

Sossin

2013

Journal of Neurophysiology

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“…Brain-enriched genes such as the classical sodium channel serving to generate the action potential upstroke (LNa v 1 (15)) is completely lacking in the snail heart. Also, the snail heart does not express the brain-enriched synaptic non-L-type calcium channel LCa v 2 (25). Note the line break in the y axis scale in Fig.…”

Section: Sodium-permeant T-type Channel Is the Only Major Sodium Currmentioning

confidence: 98%

T-type Channels Become Highly Permeable to Sodium Ions Using an Alternative Extracellular Turret Region (S5-P) Outside the Selectivity Filter

Senatore

Guan

Boone

et al. 2014

Journal of Biological Chemistry

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112

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Background: Ion selectivity of voltage-gated channels is governed by selectivity filters. Results: Alternative turret region in domain II promotes highly sodium-permeable T-type channels without major changes to gating and kinetic features. Conclusion: T-type channels can generate variable sodium or calcium permeability by gene splicing. Significance: Ion selectivity in T-type channels can be altered using extracellular domains outside the ion selectivity filter.

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“…Synaptic membrane potential depolarization induces activation of voltagedependent calcium channels, which consequently stimulates calcium entry into presynapses with rapidly increased calcium levels at intra and presynapse sites (38,40). The rise in calcium levels is the initiating step for synaptic vesicle transport and membrane fusion release as well as for reuptake of neurotransmitters (15,32,47,76); such transient increases in synaptic calcium levels are subsequently quenched to avoid injury due to long-lasting calcium stimulation (17,20).…”

Section: Synaptic Mitochondria and Synaptic Neurotransmissionmentioning

confidence: 99%

Synaptic Mitochondrial Pathology in Alzheimer's Disease

Guo

Yan

2012

Antioxidants & Redox Signaling

128

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Significance: Synaptic degeneration, an early pathological feature in Alzheimer's disease (AD), is closely correlated to impaired cognitive function and memory loss. Recent studies suggest that involvement of amyloid-beta peptide (Ab) in synaptic mitochondrial alteration underlies these synaptic lesions. Thus, to understand the Abassociated synaptic mitochondrial perturbations would fortify our understanding of synaptic stress in the pathogenesis of AD. Recent Advances: Increasing evidence suggests that synaptic mitochondrial dysfunction is strongly associated with synaptic failure in many neurodegenerative diseases including AD. Based on recent findings in human AD subjects, AD animal models, and AD cellular models, synaptic mitochondria undergo multiple malfunctions including Ab accumulation, increased oxidative stress, decreased respiration, and compromised calcium handling capacity, all of which occur earlier than changes seen in nonsynaptic mitochondria before predominant AD pathology. Of note, the impact of Ab on mitochondrial motility and dynamics exacerbates synaptic mitochondrial alterations. Critical Issues: Synaptic mitochondria demonstrate early deficits in AD; in combination with the role that synaptic mitochondria play in sustaining synaptic functions, deficits in synaptic mitochondria may be a key factor involved in an early synaptic pathology in AD. Future Directions: The importance of synaptic mitochondria in supporting synapses and the high vulnerability of synaptic mitochondria to Ab make them a promising target of new therapeutic strategy for AD.

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G-proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage-dependent regulation of mammalian Cav2.1 and Cav2.2 channels

Cited by 21 publications

References 28 publications

Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin

Inhibition of the Aplysia sensory neuron calcium current with dopamine and serotonin

T-type Channels Become Highly Permeable to Sodium Ions Using an Alternative Extracellular Turret Region (S5-P) Outside the Selectivity Filter

Synaptic Mitochondrial Pathology in Alzheimer's Disease

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