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Cited by 47Pancreatic function and diabetesIon channel regulation and functionReceptor Mechanisms and Signaling

G protein‐dependent inhibition of L‐type Ca2+ currents by acetylcholine in mouse pancreatic B‐cells.

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Gilon, P, Yakel, J, Gromada, J, Zhu, Y, Henquin, J C, Rorsman, P·1997·The Journal of Physiology
DOI 10.1113/jphysiol.1997.sp021911PMC PMC1159337
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Abstract

1. The effect of acetylcholine (ACh) on voltage‐dependent Ca2+ currents in mouse pancreatic B‐cells was studied using the whole‐cell configuration of the patch‐clamp technique. 2. ACh (0.25‐250 microM) reversibly and dose‐dependently inhibited the Ca2+ current elicited by depolarizations from ‐80 mV to +10 mV. Maximal inhibition was observed at concentrations > 25 microM where it amounted to approximately 35%. The effect was voltage independent and prevented by atropine (10 microM) suggesting that it was mediated by muscarinic receptors. 3. The inhibitory action of ACh on the Ca2+ current was abolished when the cytoplasmic solution contained GDP beta S (2 mM) and became irreversible when the non‐hydrolysable GTP analogue GTP gamma S (10 microM) was included in the pipette. This indicates the participation of G proteins in the inhibitory effect of ACh but pretreatment of the cells with either pertussis or cholera toxin failed to prevent the effect of ACh on the Ca2+ current. 4. ACh remained equally effective as an inhibitor of the whole‐cell Ca2+ current in the presence of the L‐type Ca2+ channel agonist (‐)‐Bay K 8644 and after partial inhibition of the current by nifedipine. Addition of omega‐agatoxin IVA, omega‐conotoxin GVIA or omega‐conotoxin MVIIC neither affected the peak Ca2+ current amplitude nor the extent of inhibition produced by ACh. These pharmacological properties indicate that ACh acts by inhibiting L‐type Ca2+ channels. 5. The inhibitory action of ACh on the B‐cell Ca2+ current was not secondary to elevation of [Ca2+]i and ACh remained equally effective as an inhibitor when Ba2+ was used as the charge carrier, when [Ca2+]i was buffered to low concentrations using EGTA and under experimental conditions preventing the mobilization of Ca2+ from intracellular stores. 6. These results suggest that ACh reduces the whole‐cell Ca2+ current in the B‐cell through a G protein‐regulated, voltage‐ and Ca(2+)‐independent inhibition of L‐type Ca2+ channels.

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  • Mouse β-cells express L-type Ca2+ channels (Cacna1c and Cacna1d) and smaller amounts of N- and P/Q-type Ca2+ channels.

    “Mouse β-cells express L-type Ca2+ channels (Cacna1c and Cacna1d) and smaller amounts of N- (Cacna1b) and P/Q-type (Cacna1a) Ca2+ channels (211, 222, 603) (seem Appendix Figure 3A).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [211]

    The paper’s results on mouse pancreatic B-cells (pp. 65–76) identify the acetylcholine-sensitive current as L-type, supporting that part of the claim. They do not identify Cacna1c or Cacna1d or establish smaller amounts of N- and P/Q-type channels; the tested N- and P/Q-type channel blockers did not affect peak current amplitude. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • HCN channels may therefore contribute to the reported shortening of the interburst interval observed in β-cells of mouse islets exposed to high (50 nM) concentrations of GLP-1.

    “HCN channels may therefore contribute to the reported shortening of the interburst interval observed in β-cells (211) of mouse islets exposed to high (50 nM) concentrations of GLP-1 (238).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [211]

    The indexed paper’s title and selected references concern acetylcholine and calcium currents in mouse pancreatic B-cells. Searches for GLP-1, 50 nM, and interburst interval found no passage in our copy reporting the claimed shortening of the interburst interval. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Gilon, P., Yakel, J., Gromada, J., Zhu, Y., Henquin, J. C., & Rorsman, P.
Affiliations
Novo Nordisk (Denmark) (DK)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
1997-02-15
Volume
499
Issue
1
Pages
65-76
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.1997.sp021911
PMC
PMC1159337
OpenAlex
W2169419420
Cited by
47
References
0
Citations by year
2024: 1 · 2023: 1 · 2021: 4 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 3
FWCI
3.45
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Libraries (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
acetylcholine, L-type calcium channels, pancreatic beta cells, G proteins, muscarinic receptors, calcium current inhibition, GTP gamma S, GDP beta S, omega-conotoxin MVIIC, omega-agatoxin IVA, omega-conotoxin GVIA, intracellular calcium, atropine, nifedipine, Bay K 8644
MeSH terms
Acetylcholine, Animals, Dose-Response Relationship, Drug, Pancreas, Calcium Channels, GTP-Binding Proteins, Mice

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