alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation

Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved i...

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Veröffentlicht in:American Journal of Physiology: Cell Physiology 2002-09, Vol.283 (3), p.C1001-C1008
Hauptverfasser: Lyford, Greg L, Strege, Peter R, Shepard, Allan, Ou, Yijun, Ermilov, Leonid, Miller, Steven M, Gibbons, Simon J, Rae, James L, Szurszewski, Joseph H, Farrugia, Gianrico
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container_end_page C1008
container_issue 3
container_start_page C1001
container_title American Journal of Physiology: Cell Physiology
container_volume 283
creator Lyford, Greg L
Strege, Peter R
Shepard, Allan
Ou, Yijun
Ermilov, Leonid
Miller, Steven M
Gibbons, Simon J
Rae, James L
Szurszewski, Joseph H
Farrugia, Gianrico
description Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the alpha(1C) L-type calcium channel subunit (Ca(V)1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a beta(2) calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac alpha(1C) splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the alpha(1C) COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit.
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subjects Animals
Calcium Channels, L-Type - biosynthesis
Calcium Channels, L-Type - drug effects
Calcium Channels, L-Type - genetics
Cell Line
CHO Cells
Cloning, Molecular
Cricetinae
Enzyme Inhibitors - pharmacology
Humans
Ion Channel Gating - drug effects
Jejunum - metabolism
Kidney - cytology
Kidney - metabolism
Membrane Potentials - drug effects
Membrane Potentials - physiology
Molecular Sequence Data
Organ Specificity - physiology
Patch-Clamp Techniques
Pressure
Protein Isoforms - biosynthesis
Protein Isoforms - drug effects
Protein Isoforms - genetics
Protein Structure, Tertiary - physiology
Protein Subunits
Sequence Deletion
Signal Transduction - drug effects
Signal Transduction - physiology
Space life sciences
Stress, Mechanical
Transfection
title alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation
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