Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells
Barg, Sebastian LU ; Galvanovskis, J ; Gopel, S O ; Rorsman, Patrik LU and Eliasson, Lena LU
(2000)
In Diabetes
49(9).
p.1500-1510
- Abstract
- alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a... (More)
- alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable outward current (activating at voltages above -20 mV), a large tetrodotoxin-sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)-channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional subsets of granules were identified, and the size of the immediately releasable pool was estimated as 80 granules, or 1% of the total granule number. The maximal rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage-clamp depolarization, which is precisely the duration of Ca(2+)-influx during an action potential. Our results suggest that the secretory machinery of the alpha-cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1117032
- author
- Barg, Sebastian
LU
; Galvanovskis, J
; Gopel, S O
; Rorsman, Patrik
LU
and Eliasson, Lena
LU
- organization
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 49
- issue
- 9
- pages
- 1500 - 1510
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:10969834
- ISSN
- 1939-327X
- language
- English
- LU publication?
- yes
- id
- 430d580b-18ab-4782-84a4-6cdbb2886012 (old id 1117032)
- alternative location
- http://diabetes.diabetesjournals.org/cgi/reprint/49/9/1500
- date added to LUP
- 2016-04-01 15:44:43
- date last changed
- 2019-03-08 02:45:52
@article{430d580b-18ab-4782-84a4-6cdbb2886012,
abstract = {{alpha-Cells were identified in preparations of dispersed mouse islets by immunofluorescence microscopy. A high fraction of alpha-cells correlated with a small cell size measured as the average cell diameter (10 microm) and whole-cell capacitance (<4 pF). The alpha-cells generated action potentials at a low frequency (1 Hz) in the absence of glucose. These action potentials were reversibly inhibited by elevation of the glucose concentration to 20 mmol/l. The action potentials originated from a membrane potential more negative than -50 mV, had a maximal upstroke velocity of 5 V/s, and peaked at +1 mV. Voltage-clamp experiments revealed the ionic conductances underlying the generation of action potentials. alpha-Cells are equipped with a delayed tetraethyl-ammonium-blockable outward current (activating at voltages above -20 mV), a large tetrodotoxin-sensitive Na+ current (above -30 mV; peak current 200 pA at +10 mV), and a small Ca2+ current (above -50 mV; peak current 30 pA at +10 mV). The latter flowed through omega-conotoxin GVIA (25%)- and nifedipine-sensitive (50%) Ca(2+)-channels. Mouse alpha-cells contained, on average, 7,300 granules, which undergo Ca(2+)-induced exocytosis when the alpha-cell is depolarized. Three functional subsets of granules were identified, and the size of the immediately releasable pool was estimated as 80 granules, or 1% of the total granule number. The maximal rate of exocytosis (1.5 pF/s) was observed 21 ms after the onset of the voltage-clamp depolarization, which is precisely the duration of Ca(2+)-influx during an action potential. Our results suggest that the secretory machinery of the alpha-cell is optimized for maximal efficiency in the use of Ca2+ for exocytosis.}},
author = {{Barg, Sebastian and Galvanovskis, J and Gopel, S O and Rorsman, Patrik and Eliasson, Lena}},
issn = {{1939-327X}},
language = {{eng}},
number = {{9}},
pages = {{1500--1510}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells}},
url = {{http://diabetes.diabetesjournals.org/cgi/reprint/49/9/1500}},
volume = {{49}},
year = {{2000}},
}