Selectivity of ω-CgTx-MVIIC toxin from Conus magus on calcium currents in enteric neurons

Starodub, Alexander M.; Wood, Jackie D.

doi:10.1016/s0024-3205(99)00213-1

Cited by 21 publications

(18 citation statements)

References 15 publications

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“…The α 2 ‐adrenoceptors are the target for sympathetic nervous system modulation of synaptic transmission and R‐type Ca 2+ channels may be one target for nerve‐released noradrenaline. However, previous studies have shown that N‐ and P/Q‐type Ca 2+ channels make major contributions to the calcium entry into nerve terminals required for neurotransmitter release from myenteric neurons 14–18 . The contribution of R‐type Ca 2+ channels to the release of fast or slow excitatory synaptic transmitters in the myenteric plexus remains to be determined.…”

Section: Discussionmentioning

confidence: 96%

α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

Bian

Galligan

2007

Neurogastroenterology Motil

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Abstractα 2 -adrenoceptors inhibit Ca 2+ influx through voltage-gated Ca 2+ channels throughout the nervous system and Ca 2+ channel function is modulated following activation of some G-protein coupled receptors. We studied the specific Ca 2+ channel inhibited following α 2 -adrenoceptor activation in guinea pig small intestinal myenteric neurons. Ca 2+ currents (I Ca 2+ ) were studied using whole-cell patch clamp techniques. Changes in intracellular Ca 2+ (Δ[Ca 2+ ] i ) in nerve cell bodies and varicosities were studied using digital imaging where Ca 2+ influx was evoked by KCl (60 mM) depolarization. The α 2 -adrenoceptor agonist, UK 14,304 (0.01 − 1 μM) inhibited I Ca 2+ and Δ[Ca 2+ ] i ; maximum inhibition of I Ca 2+ was 40%. UK 14,304 did not affect I Ca 2+ in the presence of SNX-482 or NiCl 2 (R-type Ca 2+ channel antagonists). UK 14,304 inhibited I Ca 2+ in the presence of nifedipine, ω-agatoxin IVA or ω-conotoxin, inhibitors of L-, P/Q-and N-type Ca 2+ channels. UK 14,304 induced Inhibition of I Ca 2+ was blocked by pertussis toxin pretreatment (1 μg/ml for 2 hr). α 2 -Adrenoceptors couple to inhibition of R-type Ca 2+ channels via a pertussis toxin-sensitive pathway in myenteric neurons. R-type channels may be a target for the inhibitory actions of norepinephrine released from sympathetic nerves on to myenteric neurons. Keywordsα1E; Ca v2.3 ; calcium imaging; enteric nervous system; presynaptic inhibitionGastrointestinal motility is controlled in part by the enteric nervous system (ENS) and by extrinsic sympathetic nerves. The ENS provides primary control over gut function while the sympathetic innervation modulates ENS activity (1). The myenteric plexus, a division of the ENS, is particularly important for control of gastrointestinal motility (2). Using electrophysiological criteria, myenteric neurons can be classified as S or AH neurons (3) and AH neurons may be intrinsic primary afferent neurons (4). In AH neurons the action potential has a Ca 2+ shoulder that is dependent on activation of N-type Ca 2+ channels (5). Ca 2+ entering during the action potential triggers calcium release from intracellular stores (6,7). The rise in intracellular Ca 2+ then activates a Ca 2+ -dependent K + channel, causing a long-lasting afterhyperpolarization (AHP) (4,8,9). S neurons are interneurons and motorneurons (10). Although action potentials in S neurons are blocked completely by tetrodotoxin (sodium channel antagonist), they are also associated with increases in intracellular calcium that are partly dependent on activation of N-type Ca 2+ channels (11).Guinea pig myenteric neurons express multiple Ca2+ subtypes (12). The total Ca 2+ current (I Ca 2+ ) in myenteric neurons is composed of contributions of Ca 2+ influx through L-N-P/Q- and R-type Ca 2+ channels (13-18). The R-type channels make the largest contribution to the total I Ca 2+ in myenteric neurons of guinea-pig small intestine maintained in the primary culture (13). R-type Ca 2+ channels are composed of the pore forming α 1E subunit (19,20). SNX 482 (2...

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Section: Discussionmentioning

confidence: 96%

α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

Bian

Galligan

2007

Neurogastroenterology Motil

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“…In the case of classic electrical excitation, it has been shown that action potential firing correlates well with increases in [Ca 2+ ] i (Vanden Berghe et al, 2001; Michel et al, 2011; Martens et al, 2014). [Ca 2+ ] i transients in enteric neurons are mediated by various Ca 2+ channels including N-, P/Q-, L- and R-type Ca 2+ channels (Garaulet et al, 1996; Starodub and Wood, 1999; Reis et al, 2000; Smith et al, 2003; Bian et al, 2004; Bian and Galligan, 2007; Hao et al, 2011). [Ca 2+ ] i signals that we observe with GCaMP3 are unlikely to directly correspond with slow EPSPs.…”

Section: Discussionmentioning

confidence: 99%

VPAC Receptor Subtypes Tune Purinergic Neuron-to-Glia Communication in the Murine Submucosal Plexus

Fung

Boesmans

Cirillo

et al. 2017

Front. Cell. Neurosci.

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The enteric nervous system (ENS) situated within the gastrointestinal tract comprises an intricate network of neurons and glia which together regulate intestinal function. The exact neuro-glial circuitry and the signaling molecules involved are yet to be fully elucidated. Vasoactive intestinal peptide (VIP) is one of the main neurotransmitters in the gut, and is important for regulating intestinal secretion and motility. However, the role of VIP and its VPAC receptors within the enteric circuitry is not well understood. We investigated this in the submucosal plexus of mouse jejunum using calcium (Ca2+)-imaging. Local VIP application induced Ca2+-transients primarily in neurons and these were inhibited by VPAC1- and VPAC2-antagonists (PG 99-269 and PG 99-465 respectively). These VIP-evoked neural Ca2+-transients were also inhibited by tetrodotoxin (TTX), indicating that they were secondary to action potential generation. Surprisingly, VIP induced Ca2+-transients in glia in the presence of the VPAC2 antagonist. Further, selective VPAC1 receptor activation with the agonist ([K15, R16, L27]VIP(1-7)/GRF(8-27)) predominantly evoked glial responses. However, VPAC1-immunoreactivity did not colocalize with the glial marker glial fibrillary acidic protein (GFAP). Rather, VPAC1 expression was found on cholinergic submucosal neurons and nerve fibers. This suggests that glial responses observed were secondary to neuronal activation. Trains of electrical stimuli were applied to fiber tracts to induce endogenous VIP release. Delayed glial responses were evoked when the VPAC2 antagonist was present. These findings support the presence of an intrinsic VIP/VPAC-initiated neuron-to-glia signaling pathway. VPAC1 agonist-evoked glial responses were inhibited by purinergic antagonists (PPADS and MRS2179), thus demonstrating the involvement of P2Y1 receptors. Collectively, we showed that neurally-released VIP can activate neurons expressing VPAC1 and/or VPAC2 receptors to modulate purine-release onto glia. Selective VPAC1 activation evokes a glial response, whereas VPAC2 receptors may act to inhibit this response. Thus, we identified a component of an enteric neuron-glia circuit that is fine-tuned by endogenous VIP acting through VPAC1- and VPAC2-mediated pathways.

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“…The Ca v 2.1 currents are acquired during neuronal differentiation from neural crest [3]. Acetylcholine release at the peripheral neuron muscular junctions in the colon depends on calcium channels, including Ca v 2.1 channels [18]. To understand the functions of Ca v 2.1 in the rolling Nagoya mouse strain, establishing a strain with an intact Ednrb gene will be important.…”

Section: Discussionmentioning

confidence: 99%

Rolling Nagoya Mouse Strain (PROD-<i>rol</i>/<i>rol</i>) with Classic Piebald Mutation

Yoshimoto

Aoyama

Kim

et al. 2014

The Journal of Veterinary Medical Science

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Ataxic rolling Nagoya (PROD-rol/rol) mice, which carry a mutation in the α1 subunit of the Cav2.1 channel (Cacna1a) gene, were discovered in 1969. They show white spots on agouti coat and have a mutation in the piebald spotting (s) locus. However, mutation analysis of the s locus encoding the endothelin receptor type B (Ednrb) gene in PROD-rol/rol mice had not been performed. Here, we examined the genomic and mRNA sequences of the Ednrb gene in PROD-rol/rol and wild-type rolling Nagoya (PROD-s/s) and studied the expression patterns of Ednrb and Cacna1a genes in these mice in comparison with C57BL/6J mice. Polymerase chain reaction analyses revealed two silent nucleotide substitutions in the coding region and insertion of a retroposon-like element in intron 1 of the Ednrb gene. Expression analyses demonstrated similar localizations and levels of Ednrb and Cacna1a expression in the colon between PROD-rol/rol and PROD-s/s mice, but the expression levels of both genes were diminished compared with C57BL/6J mice. Microsatellite genotyping showed that at least particular regions of chromosome 14 proximal to the Ednrb locus of the PROD strain were derived from Japanese fancy piebald mice. These results indicated that PROD-rol/rol mice have two mutant genes, Ednrb and Cacna1a. As no PROD strain had an intact Ednrb gene, using congenic rolling mice would better serve to examine rolling Nagoya-type Cav2.1 channel dysfunctions.

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Selectivity of ω-CgTx-MVIIC toxin from Conus magus on calcium currents in enteric neurons

Cited by 21 publications

References 15 publications

α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

VPAC Receptor Subtypes Tune Purinergic Neuron-to-Glia Communication in the Murine Submucosal Plexus

Rolling Nagoya Mouse Strain (PROD-<i>rol</i>/<i>rol</i>) with Classic Piebald Mutation

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Selectivity of ω-CgTx-MVIIC toxin from Conus magus on calcium currents in enteric neurons

Cited by 21 publications

References 15 publications

α2‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

α2‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

VPAC Receptor Subtypes Tune Purinergic Neuron-to-Glia Communication in the Murine Submucosal Plexus

Rolling Nagoya Mouse Strain (PROD-<i>rol</i>/<i>rol</i>) with Classic Piebald Mutation

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α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons

α₂‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons