Regulation of N-type calcium channels by G-proteins: Multiple pathways to control calcium entry into neurons

Weiss, Norbert

doi:10.4161/chan.3.4.9255

Cited by 6 publications

(7 citation statements)

References 7 publications

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“…Similar observations have been reported for m-and d-opioid receptors transiently expressed with Ca v 2.2 channel in tsA201 cells, although the existence of these protein complexes remains to be explored in native conditions (Chee et al, 2008;Evans et al, 2010). Also, a physical interaction exists between Ca v 2.2 channels and dopamine D1 and D2 receptors and requires other channel structural determinants, including the II-III intracellular linker Kisilevsky and Zamponi, 2008;Weiss, 2009). Although the existence of Ca v 2-GPCR signaling complexes is unambiguous, the physiologic relevance of these interactions is not fully understood.…”

Section: Voltage-independent Inhibition Of Ca V 2 Channelssupporting

confidence: 76%

“…Interestingly, the binding determinant of Gbg dimer in the carboxy-terminal region of Ca v 2 channels is localized close to the binding domain of Gao on Ca v 2.1 and Ca v 2.2 subunits (Furukawa et al, 1998b) and Gaq on the Ca v 2.2 subunit (Simen et al, 2001) (Fig. 4A), suggesting that the carboxy-terminal region could be involved in the functional and biochemical coupling of Ca v 2 channels with the GPCR via the Ga/bg trimmer (Kitano et al, 2003;Beedle et al, 2004;Weiss, 2009). Paradoxically, the importance of the carboxy-terminal region of Ca v 2 channels in the direct regulation by G proteins was poorly investigated compared with the intensive work that was done for the I-II loop and the aminoterminal region.…”

Section: Regulation Of Calcium Channels By G Proteinsmentioning

confidence: 99%

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G Protein Regulation of Neuronal Calcium Channels: Back to the Future

Proft

Weiss

2014

Mol Pharmacol

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Neuronal voltage-gated calcium channels have evolved as one of the most important players for calcium entry into presynaptic endings responsible for the release of neurotransmitters. In turn, and to fine-tune synaptic activity and neuronal communication, numerous neurotransmitters exert a potent negative feedback over the calcium signal provided by G protein-coupled receptors. This regulation pathway of physiologic importance is also extensively exploited for therapeutic purposes, for instance in the treatment of neuropathic pain by morphine and other m-opioid receptor agonists. However, despite more than three decades of intensive research, important questions remain unsolved regarding the molecular and cellular mechanisms of direct G protein inhibition of voltage-gated calcium channels. In this study, we revisit this particular regulation and explore new considerations.

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Section: Voltage-independent Inhibition Of Ca V 2 Channelssupporting

confidence: 76%

Section: Regulation Of Calcium Channels By G Proteinsmentioning

confidence: 99%

G Protein Regulation of Neuronal Calcium Channels: Back to the Future

Proft

Weiss

2014

Mol Pharmacol

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“…In the GPCR heterocomplex, the subunit G (q) activates PLC, stimulates the release of Ca 2+ from the endoplasmic reticulum and increases the intracellular levels of Ca 2+ . Calmodulin binds to Ca 2+ , activates downstream regulators and mediates biological activities of several calcium‐sensitive enzymes, ion channels and other proteins (Farooqui, ; Weiss, ; Farooqui, ). The relationship between OAR α1 and calmodulin in modulating olfactory attraction is consistent with the function of the OA‐OAR α1 pathway in mediating behavioural responses through Ca 2+ signalling.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, previous reports have confirmed that Ca 2+ /calmodulin‐dependent protein kinase II regulates olfactory reaction and sensitivity in insects (Lohr et al ., ). The calmodulin signalling pathway mediates the sensitivity of chemosensory signalling in olfactory bulbs (Weiss, ). Our findings of calmodulin in modulating locust olfactory attraction are consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Calmodulin as a downstream gene of octopamine‐OAR α1 signalling mediates olfactory attraction in gregarious locusts

Yang

et al. 2016

Insect Molecular Biology

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The migratory locust (Locusta migratoria) shows aggregative traits in nymph marching bands and swarm formations through mutual olfactory attraction of conspecifics. However, olfactory preference in different nymph stages in gregarious locusts is not sufficiently explored. In this study, we found that the nymph olfactory preference for gregarious volatiles exhibited obvious variations at different developmental stages. The gregarious locusts show attractive response to conspecific volatiles from the third stadium. Transcriptome comparison between third- and fourth-stadium nymphs showed that the G protein-coupled receptor (GPCR) pathways are significantly enriched. Amongst the genes present in GPCR pathways, the expression level of calmodulin in locust brains significantly increased from the third- to the fourth-stadium nymphs. Amongst the four octopamine receptors (OARs) belonging to the GPCR family, only OAR α1 showed similar expression patterns to those of calmodulin, and knockdown of OAR α1 reduced the expression level of calmodulin. RNA interference of calmodulin decreased locomotion and induced the loss of olfactory attraction in gregarious locusts. Moreover, the activation of OAR α1 in calmodulin-knockdown locusts did not induce olfactory attraction of the nymphs to gregarious volatiles. Thus, calmodulin as a downstream gene of octopamine-OAR α1 (OA-OAR α1) signalling mediates olfactory attraction in gregarious locusts. Overall, this study provides novel insights into the mechanism of OA-OAR α1 signalling involved in olfactory attraction of gregarious locusts.

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“…As well, N-type Ca 2+ channels are heavily clustered at synaptic sites associated with exocytotic proteins and a large body of work suggests that this channel controls functional coupling between action potentials and evoked neurotransmitter release from nociceptive terminals (Altier et al, 2007; Altier and Zamponi, 2004; Snutch, 2005; Zamponi et al, 2009). It is also well established that N-type Ca 2+ channels are strongly regulated by G protein coupled receptors that allow precise control of neurotransmitter release through inhibition of the N-type channel (Currie, 2010; Weiss, 2009). …”

Section: Discussionmentioning

confidence: 99%

Sumatriptan inhibition of N-type calcium channel mediated signaling in dural CGRP terminal fibres

2012

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The selective 5-HT1 receptor agonist sumatriptan is an effective therapeutic for migraine pain yet the antimigraine mechanisms of action remain controversial. Pain-responsive fibres containing calcitonin gene-related peptide (CGRP) densely innervating the cranial dura mater are widely believed to be an essential anatomical substrate for the development of migraine pain. 5HT1 receptors in the dura colocalize with CGRP fibres in high density and thus provide a possible peripheral site of action for sumatriptan. In the present study, we used high-resolution optical imaging selectively within individual mouse dural CGRP nociceptive fibre terminations and found that application of sumatriptan caused a rapid, reversible dose-dependent inhibition in the amplitude of single action potential evoked Ca2+ transients. Pre-application of the 5-HT1 antagonist GR127935 or the selective 5-HT1D antagonist BRL 15572 prevented inhibition while the selective 5-HT1B antagonist SB 224289 did not, suggesting this effect was mediated selectively through the 5-HT1D receptor subtype. Sumatriptan inhibition of the action potential evoked Ca2+ signaling was mediated selectively through N-type Ca2+ channels. Although the T-type Ca2+ channel accounted for a greater proportion of the Ca2+ signal it did not mediate any of the sumatriptan inhibition. Our findings support a peripheral site of action for sumatriptan in inhibiting the activity of dural pain fibres selectively through a single Ca2+ channel subtype. This finding adds to our understanding of the mechanisms that underlie the clinical effectiveness of 5HT1 receptor agonists such as sumatriptan and may provide insight for the development of novel peripherally targeted therapeutics for mitigating the pain of migraine.

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Regulation of N-type calcium channels by G-proteins: Multiple pathways to control calcium entry into neurons

Cited by 6 publications

References 7 publications

G Protein Regulation of Neuronal Calcium Channels: Back to the Future

G Protein Regulation of Neuronal Calcium Channels: Back to the Future

Calmodulin as a downstream gene of octopamine‐OAR α1 signalling mediates olfactory attraction in gregarious locusts

Sumatriptan inhibition of N-type calcium channel mediated signaling in dural CGRP terminal fibres

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