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Physiology 23: 23-31, 2008; doi:10.1152/physiol.00034.2007
1548-9213/08 $8.00
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Physiology, Vol. 23, No. 1, 23-31, February 2008
© 2008 Int. Union Physiol. Sci./Am. Physiol. Soc.

REVIEW

A New Trick for an Old Dogma: ENaC Proteins as Mechanotransducers in Vascular Smooth Muscle

Heather A. Drummond1, Samira C. Grifoni1 and Nikki L. Jernigan2

1 Department of Physiology and Biophysics, and Center for Excellence in Cardio-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi; and
2 Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, hdrummond{at}physiology.umsmed.edu

Myogenic constriction is a vasoconstriction of blood vessels to increases in perfusion pressure. In renal preglomerular vasculature, it is an established mechanism of renal blood flow autoregulation. Recently, myogenic constriction has been identified as an important protective mechanism, preventing the transmission of systemic pressure to the fragile glomerular vasculature. Although the signal transduction pathways mediating vasoconstriction are well known, how the increases in pressure trigger vasoconstriction is unclear. The response is initiated by pressure-induced stretch of the vessel wall and thus is dependent on mechanical signaling. The identity of the sensor detecting VSMC stretch is unknown. Previous studies have considered the role of extracellular matrix-integrin interactions, ion conduction units (channels and/or transporters), and the cytoskeleton as pressure detectors. Whether, and how, these structures fit together in VSMCs is poorly understood. However, a model of mechanotransduction in the nematode Caenorhadbditis elegans (C. elegans) has been established that ties together extracellular matrix, ion channels, and cytoskeletal proteins into a large mechanosensing complex. In the C. elegans mechanotransducer model, a family of evolutionarily conserved proteins, referred to as the DEG/ENaC/ASIC family, form the ion-conducting pore of the mechanotransducer. Members of this protein family are expressed in VSMC where they may participate in pressure detection. This review will address how the C. elegans mechanotransducer model can be used to model pressure detection in mammalian VSMCs and provide a new perspective to pressure detection in VSMCs.







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