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

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 se...

Full description

Saved in:
Bibliographic Details
Published in:Pflügers Archiv 1995-12, Vol.431 (2), p.272
Main Authors: Barnett, D W, Pressel, D M, Misler, S
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Action Potentials - physiology
Amiloride - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Channels - drug effects
Calcium Channels - physiology
Diuretics - pharmacology
Electrophysiology
Humans
In Vitro Techniques
Insulin - metabolism
Ion Channel Gating - drug effects
Ion Channel Gating - physiology
Islets of Langerhans - cytology
Islets of Langerhans - metabolism
Islets of Langerhans - physiology
Membrane Potentials - drug effects
Membrane Potentials - physiology
Nifedipine - pharmacology
Patch-Clamp Techniques
Sodium Channels - drug effects
Sodium Channels - physiology
Tetrodotoxin - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0031-6768
DOI:10.1007/BF00410201