Korean J Physiol Pharmacol.  2020 Jul;24(4):287-298. 10.4196/kjpp.2020.24.4.287.

Endothelial Ca²⁺ signaling-dependent vasodilation through transient receptor potential channels

• Hong KS
• Lee MG

• KMID: 2503322
• DOI: http://doi.org/10.4196/kjpp.2020.24.4.287

Abstract

Ca²⁺ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca²⁺ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca²⁺ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K⁺ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca²⁺ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca²⁺- permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca²⁺-sensitive K⁺ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca²⁺ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca²⁺ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

Keyword

Calcium signaling; Endothelium; Gap Junctions; Ion channels; Microcirculation; Vasodilation

Figure

• 

  Fig. 1 Transient receptor potential (TRP) channel-mediated endothelium-dependent hyperpolarization (EDH) and vasodilation. TRP channels (e.g., representatively TRPV4 channels) are placed myoendothelial projections (MEPs) that are extensions of endothelial cells (ECs) through internal elastic lamina to contact adjacent vascular smooth muscle cells (VSMCs). Localized Ca2+ entry through endothelial TRP channels stimulate intermediate/small conductance Ca2+-sensitive potassium (IKCa/SKCa) channels and in turn results in EDH via K+ ion efflux. EDH is transmitted to adjacent VSMCs through myoendothelial gap junctions (MEGJs) comprising of two hemi-channels, which initiates VSMC hyperpolarization. The altered membrane potential of VSMCs suppresses voltage-dependent Ca2+ channels (VDCCs) and evokes vasodilation.

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