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Cited by 98Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

CaM kinase II‐dependent mobilization of secretory granules underlies acetylcholine‐induced stimulation of exocytosis in mouse pancreatic B‐cells

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Gromada, Jesper, Høy, Marianne, Renström, Erik, Bokvist, Krister, Eliasson, Lena, Göpel, Sven, Rorsman, Patrik·1999·The Journal of Physiology
DOI 10.1111/j.1469-7793.1999.0745p.xPMC PMC2269462
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Abstract

1. Measurements of cell capacitance were used to investigate the mechanisms by which acetylcholine (ACh) stimulates Ca2+-induced exocytosis in single insulin-secreting mouse pancreatic B-cells. 2. ACh (250 microM) increased exocytotic responses elicited by voltage-clamp depolarizations 2.3-fold. This effect was mediated by activation of muscarinic receptors and dependent on elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i) attributable to mobilization of Ca2+ from intracellular stores. The latter action involved interference with the buffering of [Ca2+]i and the time constant (tau) for the recovery of [Ca2+]i following a voltage-clamp depolarization increased 5-fold. As a result, Ca2+ was present at concentrations sufficient to promote the replenishment of the readily releasable pool of granules (RRP; > 0.2 microM) for much longer periods in the presence than in the absence of the agonist. 3. The effect of Ca2+ on exocytosis was mediated by activation of CaM kinase II, but not protein kinase C, and involved both an increased size of the RRP from 40 to 140 granules and a decrease in tau for the refilling of the RRP from 31 to 19 s. 4. Collectively, the effects of ACh on the RRP and tau result in a > 10-fold stimulation of the rate at which granules are supplied for release.

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Crossref · 10.1111/j.1469-7793.1999.0745p.x

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  • Granule mobilization is accelerated by Ca2+ via activation of CAMKII.

    “Granule mobilization is accelerated by cAMP (via activation of PKA) (545) and by Ca2+ (via activation of CAMKII) (241).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [241]

  • Following depletion of the RRP, refilling of the RRP follows an exponential time course with a time constant of ~30 s.

    “Capacitance measurements have revealed that following depletion of the RRP - as evidenced by the cessation of exocytosis despite continued stimulation - refilling of the RRP follows an exponential time course with a time constant of ~30 s (241).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [241]

  • When β-cells were exposed to forskolin or to ACh, the RRP increased 3- to 4-fold relative to that seen under control conditions.

    “When β-cells were exposed to forskolin (to increase cAMP and activate both PKA and Epac2) or to ACh (to mobilize intracellular Ca2+ and activate CAMKII), the RRP increased 3- to 4-fold relative that seen under control conditions (241, 545).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [241]

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Cited by

Sorted by citations

Authors
Gromada, J., Høy, M., Renström, E., Bokvist, K., Eliasson, L., Göpel, S., & Rorsman, P.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Lund University (SE)
Corresponding author
Gromada, Jesper
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
1999-08
Volume
518
Issue
3
Pages
745-759
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1111/j.1469-7793.1999.0745p.x
PMC
PMC2269462
OpenAlex
W2135601875
Cited by
98
References
0
Citations by year
2026: 2 · 2025: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2017: 4 · 2016: 5 · 2014: 8 · 2013: 2 · 2012: 3
FWCI
5.78
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1864 d)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
  • Novo Nordisk Fonden
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
CaM kinase II, acetylcholine, exocytosis, insulin secretion, pancreatic beta cells, secretory granules, readily releasable pool, intracellular calcium stores, muscarinic receptors, calcium buffering, protein kinase C, cell membrane capacitance
MeSH terms
Acetylcholine, Animals, Calcium, Cytoplasmic Granules, Electric Conductivity, Electrophysiology, Enzyme Inhibitors, Exocytosis, Islets of Langerhans, Kinetics, Membrane Potentials, Protein Kinase C, Stimulation, Chemical, Calcium-Calmodulin-Dependent Protein Kinases, Patch-Clamp Techniques, Muscarinic Agonists, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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