Cited by 100Pancreatic function and diabetesIon channel regulation and functionIon Transport and Channel Regulation

Voltage-dependent Na+ and Ca2+ currents in human pancreatic islet ?-cells: evidence for roles in the generation of action potentials and insulin secretion

Barnett, David W., Pressel, David M., Misler, Stanley·1995·Pfl�gers Archiv European Journal of Physiology

Abstract

We describe three voltage-dependent inward currents in human pancreatic beta-cells. First, a rapidly inactivating Na+ current, blocked by tetrodotoxin (TTX) is seen upon brief depolarization to or beyond -40 mV. Second, a transient, low-voltage-activated (LVA), amiloride-blockable Ca2+ current is seen upon depolarization to or beyond -55 mV; it inactivates within less than 1s of sustained depolarization to -40 mV. Third, a more sustained, high-voltage-activated (HVA) Ca2+ current, which shows variable sensitivity to dihydropyridines is seen upon depolarization to or beyond -40 mV, and thereafter slowly inactivates over a time course of many seconds. Our pharmacological evidence suggests that all three currents contribute to action potential initiation and upstroke when the background membrane potential (Vm) is equal or negative to -45 to -40 mV, a situation often induced by glucose concentrations (5-6 mM) in the range of those seen post-prandially. Consistent with this, TTX drastically reduces both transient and sustained insulin secretion in the presence of 5-6 mM glucose, but has little effect in 10 mM glucose, at which concentration cells rapidly depolarize to approximately -35 mV, a Vm sufficient to rapidly inactivate Na+ and LVA Ca2+ currents.

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Crossref · 10.1007/bf00410201

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  • TTX reduces insulin secretion in human β-cells, with its effect particularly strong at 6 mM glucose and weaker at 10-20 mM glucose.

    “Furthermore, TTX reduces insulin secretion: its effect is particularly strong at glucose concentrations just above the threshold for GIIS (6 mM) but is weaker at higher (10-20 mM) concentrations (52, 90) (see Figure 13C-D).”
  • Human β-cells (unlike mouse β-cells) are equipped with T-type Ca2+-channels that activate at membrane potentials as negative as -60 mV.

    “Second, human β-cells (unlike mouse β-cells) are equipped with T-type Ca2+-channels that activate at membrane potentials as negative as -60 mV (52, 90).”
  • Na+ channels play a particularly important role at glucose concentrations just above the threshold for triggering electrical activity in human β-cells.

    “Na+ channels play a particularly important role at glucose concentrations just above the threshold for triggering electrical activity (52, 90).”
  • The membrane potential during interspike intervals in human β-cells may be as negative as -60 mV at 6 mM glucose, but is between -50 and -40 mV at 10 mM glucose or above.

    “This may be seen from the fact that the membrane potential during the interspike intervals may be as negative as -60 mV at 6 mM glucose, (89), but is between -50 and -40 mV at 10 mM glucose or above (52) (Figure 6 and schematic in Figure 13C-D).”

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Authors
Barnett, D. W., Pressel, D. M., & Misler, S.
Affiliations
Washington University in St. Louis (US)
Venue
Pfl�gers Archiv European Journal of Physiology
Published
1995-12
Volume
431
Issue
2
Pages
272-282
ISSN
  • 0031-6768 (ISSN-L)
  • 1432-2013
OpenAlex
W1969252369
Cited by
100
References
0
Citations by year
2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2019: 2 · 2018: 10 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 13 · 2013: 6 · 2012: 1
FWCI
1.72
Type
journal article
Language
en
Open access
closed
Locations
  • Pflügers Archiv - European Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk037380-12)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-37380)
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 › Ion Transport and Channel Regulation
Keywords
pancreatic beta cells, voltage-dependent sodium current, low-voltage-activated calcium current, high-voltage-activated calcium current, action potential generation, insulin secretion, tetrodotoxin, amiloride, dihydropyridines, membrane potential, glucose concentration, postprandial blood glucose
MeSH terms
Action Potentials, Amiloride, Calcium Channel Blockers, Diuretics, Electrophysiology, Humans, Insulin, Islets of Langerhans, Membrane Potentials, Nifedipine, Tetrodotoxin, Calcium Channels, Sodium Channels, Ion Channel Gating, Patch-Clamp Techniques, In Vitro Techniques

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