CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells
Gromada, Jesper ; Hoy, Marianne ; Renström, Erik LU ; Bokvist, Krister ; Eliasson, Lena LU
; Göpel, Sven
LU
and Rorsman, Patrik
LU
(1999)
In Journal of Physiology
518(3).
p.745-759
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1114164
- author
- Gromada, Jesper
; Hoy, Marianne
; Renström, Erik
LU
; Bokvist, Krister
; Eliasson, Lena
LU
; Göpel, Sven
LU
and Rorsman, Patrik
LU
- organization
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Physiology
- volume
- 518
- issue
- 3
- pages
- 745 - 759
- publisher
- The Physiological Society
- external identifiers
-
- pmid:10420011
- scopus:0033178286
- ISSN
- 1469-7793
- language
- English
- LU publication?
- yes
- id
- 912c1127-7ccc-4eb2-a839-818ce8261788 (old id 1114164)
- alternative location
- http://jp.physoc.org/cgi/content/full/518/3/745
- date added to LUP
- 2016-04-01 15:23:41
- date last changed
- 2022-02-19 23:09:53
@article{912c1127-7ccc-4eb2-a839-818ce8261788,
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.}},
author = {{Gromada, Jesper and Hoy, Marianne and Renström, Erik and Bokvist, Krister and Eliasson, Lena and Göpel, Sven and Rorsman, Patrik}},
issn = {{1469-7793}},
language = {{eng}},
number = {{3}},
pages = {{745--759}},
publisher = {{The Physiological Society}},
series = {{Journal of Physiology}},
title = {{CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells}},
url = {{http://jp.physoc.org/cgi/content/full/518/3/745}},
volume = {{518}},
year = {{1999}},
}