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Canonical TRP channels and mechanotransduction: from physiology to disease states

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Abstract

Mechano-gated ion channels play a key physiological role in cardiac, arterial, and skeletal myocytes. For instance, opening of the non-selective stretch-activated cation channels in smooth muscle cells is involved in the pressure-dependent myogenic constriction of resistance arteries. These channels are also implicated in major pathologies, including cardiac hypertrophy or Duchenne muscular dystrophy. Seminal work in prokaryotes and invertebrates highlighted the role of transient receptor potential (TRP) channels in mechanosensory transduction. In mammals, recent findings have shown that the canonical TRPC1 and TRPC6 channels are key players in muscle mechanotransduction. In the present review, we will focus on the functional properties of TRPC1 and TRPC6 channels, on their mechano-gating, regulation by interacting cytoskeletal and scaffolding proteins, physiological role and implication in associated diseases.

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Abbreviations

SACs:

Stretch-activated cation channels

MscL:

Bacterial mechano-sensitive large conductance channel

TRP:

Transient receptor potential channels

TRPC:

Canonical TRP channel

FSGS:

Familial focal segmental glomerulosclerosis

DMD:

Duchenne muscular dystrophy

SOCs:

Store-operated ion channels

ER:

Endoplasmic reticulum

STIM1:

Stromal interacting molecule 1

Orai proteins:

The pore-forming components of CRAC channels

RNA:

Ribonucleic acid

ROCs:

Receptor-operated channels

DAG:

Diacylglycerol

GsMTx-4:

Grammostola spatulata toxin inhibiting SACs

AT1R:

Angiotensin II type 1 receptor

Ang II:

Angiotensin II

G protein:

GTP-binding protein

PLC:

Phospholipase C

GPCR:

G protein-coupled receptor

TMD:

Transmembrane domain

M5R:

Muscarinic type 5 receptor

H1R:

Histamine type 1 receptor

ETAR:

Endothelin receptor

V1AR:

Vasopressin type 1 receptor

A7R5:

Rat vascular smooth muscle cell line

HETE:

Hydroxyeicosatetraenoic acid

MR:

Myogenic response

VSMCs:

Vascular smooth muscle cells

MEF:

Mechanoelectric feedback

TREK channels:

Mechano-gated K2P channels

OAG:

1-oleoyl-2-acetyl-sn-glycerol

MHC:

Myosin heavy chain

NFAT:

Nuclear factor of activated T cells

TAC:

Transverse aortic constriction

ATG:

Angiotensinogen

CAV:

Caveolins

eNOS:

Endothelial nitric-oxide synthase

FlnA:

Filamin A

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Acknowledgements

We are grateful to the ANR 2005 cardiovasculaire-obésité-diabète, to the ANR 2008 du gène à la physiopathologie, to the Association for information and research on genetic kidney disease France, to the Fondation del Duca, to the Human Frontier Science Program Organization-long term fellowship, to the Fondation de la recherche médicale, to the Fondation de France, to the Fondation de recherche sur l’hypertension artérielle, to the Fédération pour la recherche sur le cerveau, to Société Générale AM, to the Université of Nice Sophia Antipolis and to the CNRS for financial support. We are grateful to Dr. Sophie Demolombe for critical reading of this manuscript.

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  1. IPMC-CNRS, Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560, Valbonne, France

    Amanda Patel, Reza Sharif-Naeini, Joost R. H. Folgering, Delphine Bichet, Fabrice Duprat & Eric Honoré

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  1. Amanda Patel
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  3. Joost R. H. Folgering
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  4. Delphine Bichet
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  5. Fabrice Duprat
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  6. Eric Honoré
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Correspondence to Eric Honoré.

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Patel, A., Sharif-Naeini, R., Folgering, J.R.H. et al. Canonical TRP channels and mechanotransduction: from physiology to disease states. Pflugers Arch - Eur J Physiol 460, 571–581 (2010). https://doi.org/10.1007/s00424-010-0847-8

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  • DOI: https://doi.org/10.1007/s00424-010-0847-8

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