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Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

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ABSTRACT

The vascular endothelium is a broadly distributed and highly specialized organ. The endothelium has a number of functions including the control of blood vessels diameter through the production and release of potent vasoactive substances or direct electrical communication with underlying smooth muscle cells, regulates the permeability of the vascular barrier, stimulates the formation of new blood vessels, and influences inflammatory and thrombotic processes. Endothelial cells that make up the endothelium express a variety of cell‐surface receptors and ion channels on the plasma membrane that are capable of detecting circulating hormones, neurotransmitters, oxygen tension, and shear stress across the vascular wall. Changes in these stimuli activate signaling cascades that initiate an appropriate physiological response. Increases in the global intracellular Ca2+ concentration and localized Ca2+ signals that occur within specialized subcellular microdomains are fundamentally important components of many signaling pathways in the endothelium. The transient receptor potential (TRP) channels are a superfamily of cation‐permeable ion channels that act as a primary means of increasing cytosolic Ca2+ in endothelial cells. Consequently, TRP channels are vitally important for the major functions of the endothelium. In this review, we provide an in‐depth discussion of Ca2+‐permeable TRP channels in the endothelium and their role in vascular regulation. © 2019 American Physiological Society. Compr Physiol 9:1249‐1277, 2019.

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Figure 1. Figure 1. Mechanism of endothelium‐dependent dilation. Upon agonist stimulation, endothelial nitric oxide synthase (eNOS) activity increases to generate nitric oxide (NO). NO diffuses across the internal elastic lamina (IEL) to relax the underlying smooth muscle cells (SMC). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) enzymes to produce prostaglandin H2 (PGH2). In turn, this is converted to prostacyclin (PGI2) by prostacyclin synthase (PS), and mediates relaxation through the prostacyclin receptor (IP). Endothelial cell plasma membrane hyperpolarization generated by K+ efflux (ΔEm) spreads through myoendothelial gap junctions (MEGJ) to promote endothelium‐dependent hyperpolarization (EDH) and relaxation. Several other factors, collectively termed as endothelium‐derived hyperpolarizing factor (EDHF), hyperpolarizes smooth muscle cells to evoke relaxation.


Figure 1. Mechanism of endothelium‐dependent dilation. Upon agonist stimulation, endothelial nitric oxide synthase (eNOS) activity increases to generate nitric oxide (NO). NO diffuses across the internal elastic lamina (IEL) to relax the underlying smooth muscle cells (SMC). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) enzymes to produce prostaglandin H2 (PGH2). In turn, this is converted to prostacyclin (PGI2) by prostacyclin synthase (PS), and mediates relaxation through the prostacyclin receptor (IP). Endothelial cell plasma membrane hyperpolarization generated by K+ efflux (ΔEm) spreads through myoendothelial gap junctions (MEGJ) to promote endothelium‐dependent hyperpolarization (EDH) and relaxation. Several other factors, collectively termed as endothelium‐derived hyperpolarizing factor (EDHF), hyperpolarizes smooth muscle cells to evoke relaxation.

 

Teaching Material

P. Thakore, S. Earley. Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling. Compr Physiol 9: 2019, 1247-1275.

Didactic Synopsis

Major Teaching Points:

  1. The primary function of the vascular endothelium involves:
    1. Regulating vascular tone
    2. Maintaining the vascular barrier
    3. Angiogenesis
    4. Control of the inflammatory response
    5. Anti-thrombosis
  2. Understand that Ca2+ is key signaling messenger in mediating a physiological response
  3. Differences in structural and biophysical properties of TRP channels
  4. Ca2+ influx through TRP channels are important in maintaining normal endothelium function

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1 Teaching Points: Endothelium dependent relaxation of underlying smooth muscle occurs through increased synthesis of nitric oxide and prostacyclin, endothelium-dependent hyperpolarization that propagates to smooth muscle cells, and a collection of other factors termed endothelium-derived hyperpolarizing factor.

 


Related Articles:

TRP Channels
Molecular Mechanism of TRP Channels
Teaching Material

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How to Cite

Pratish Thakore, Scott Earley. Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling. Compr Physiol 2019, 9: 1249-1277. doi: 10.1002/cphy.c180034