Differential regulation of calcium channel coding genes by prolonged depolarization
(2007) In Neurochemistry International 50(2). p.395-403- Abstract
Calcium channels must be subjected to a very precise regulation in order to preserve cell function and viability. Voltage gated calcium channels (VGCC) represent the main pathway for calcium entry in excitable cells. This explains why depolarization induces a rapid-onset and short-term inactivation of calcium currents. Contrarily to this well-documented mechanism to maintain calcium below toxic levels, the regulatory pathways inducing longer-lasting changes and cell surface expression of functional calcium channels are largely unknown. Since calcium is a main player in the activity-dependent regulation of many genes, we hypothesize that calcium channel coding genes could be also subjected to activity-dependent regulation. We have used... (More)
Calcium channels must be subjected to a very precise regulation in order to preserve cell function and viability. Voltage gated calcium channels (VGCC) represent the main pathway for calcium entry in excitable cells. This explains why depolarization induces a rapid-onset and short-term inactivation of calcium currents. Contrarily to this well-documented mechanism to maintain calcium below toxic levels, the regulatory pathways inducing longer-lasting changes and cell surface expression of functional calcium channels are largely unknown. Since calcium is a main player in the activity-dependent regulation of many genes, we hypothesize that calcium channel coding genes could be also subjected to activity-dependent regulation. We have used prolonged depolarization to analyze the effects of sustained intracellular calcium elevation on the mRNAs coding for the different alpha(1) pore-forming subunits of the calcium channels expressed in chromaffin cells. Our findings reveal that persistent depolarization is accompanied by a prolonged intracellular calcium elevation and reduction of calcium current. This calcium current inhibition could be mediated, at least partially, by the downregulation of the mRNAs coding for several alpha(1) subunits. Thus, we show here that depolarization inhibits the expression of Ca(V)1.1, Ca(V)1.2, Ca(V)1.3, Ca(V)2.2 and Ca(V)2.3 mRNAs, while the Ca(V)2.1 mRNA remains unmodified. Moreover, such downregulation of channels depends on calcium entry through the L-type calcium channel, as both mRNA and calcium current changes induced by depolarization are abrogated by L-type channel specific blockers.
(Less)
- author
- Benavides, A ; Pastor, D ; Fradejas, N ; Tornero, D LU and Calvo, S
- publishing date
- 2007-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Benzimidazoles, Calcium, Calcium Channel Blockers, Calcium Channels, Calcium Channels, L-Type, Cattle, Cells, Cultured, Chromaffin Cells, DNA, Complementary, Down-Regulation, Electrophysiology, Fluorescent Dyes, Gene Expression Regulation, Indicators and Reagents, L-Lactate Dehydrogenase, Membrane Potentials, Nifedipine, Organic Chemicals, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction
- in
- Neurochemistry International
- volume
- 50
- issue
- 2
- pages
- 9 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:17056155
- scopus:33846252387
- ISSN
- 0197-0186
- DOI
- 10.1016/j.neuint.2006.09.013
- language
- English
- LU publication?
- no
- id
- 1aa7c33d-639a-4527-af59-af0df26f2e5a
- date added to LUP
- 2016-04-11 15:23:09
- date last changed
- 2024-01-04 01:16:54
@article{1aa7c33d-639a-4527-af59-af0df26f2e5a,
abstract = {{<p>Calcium channels must be subjected to a very precise regulation in order to preserve cell function and viability. Voltage gated calcium channels (VGCC) represent the main pathway for calcium entry in excitable cells. This explains why depolarization induces a rapid-onset and short-term inactivation of calcium currents. Contrarily to this well-documented mechanism to maintain calcium below toxic levels, the regulatory pathways inducing longer-lasting changes and cell surface expression of functional calcium channels are largely unknown. Since calcium is a main player in the activity-dependent regulation of many genes, we hypothesize that calcium channel coding genes could be also subjected to activity-dependent regulation. We have used prolonged depolarization to analyze the effects of sustained intracellular calcium elevation on the mRNAs coding for the different alpha(1) pore-forming subunits of the calcium channels expressed in chromaffin cells. Our findings reveal that persistent depolarization is accompanied by a prolonged intracellular calcium elevation and reduction of calcium current. This calcium current inhibition could be mediated, at least partially, by the downregulation of the mRNAs coding for several alpha(1) subunits. Thus, we show here that depolarization inhibits the expression of Ca(V)1.1, Ca(V)1.2, Ca(V)1.3, Ca(V)2.2 and Ca(V)2.3 mRNAs, while the Ca(V)2.1 mRNA remains unmodified. Moreover, such downregulation of channels depends on calcium entry through the L-type calcium channel, as both mRNA and calcium current changes induced by depolarization are abrogated by L-type channel specific blockers.</p>}},
author = {{Benavides, A and Pastor, D and Fradejas, N and Tornero, D and Calvo, S}},
issn = {{0197-0186}},
keywords = {{Animals; Benzimidazoles; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Cattle; Cells, Cultured; Chromaffin Cells; DNA, Complementary; Down-Regulation; Electrophysiology; Fluorescent Dyes; Gene Expression Regulation; Indicators and Reagents; L-Lactate Dehydrogenase; Membrane Potentials; Nifedipine; Organic Chemicals; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction}},
language = {{eng}},
number = {{2}},
pages = {{395--403}},
publisher = {{Elsevier}},
series = {{Neurochemistry International}},
title = {{Differential regulation of calcium channel coding genes by prolonged depolarization}},
url = {{http://dx.doi.org/10.1016/j.neuint.2006.09.013}},
doi = {{10.1016/j.neuint.2006.09.013}},
volume = {{50}},
year = {{2007}},
}