Flow-Dependent Modulation of Endothelial Ca<sup>2+</sup> Dynamics by Small Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in Mouse Carotid Arteries
Background: Small conductance Ca<sup>2+</sup> activated K<sup>+</sup> channels (K<sub>Ca</sub>2.3) are important regulators of vascular function. They provide Ca<sup>2+</sup>-dependent hyperpolarization of the endothelial membrane potential, promoting...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/12/2900 |
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| Summary: | Background: Small conductance Ca<sup>2+</sup> activated K<sup>+</sup> channels (K<sub>Ca</sub>2.3) are important regulators of vascular function. They provide Ca<sup>2+</sup>-dependent hyperpolarization of the endothelial membrane potential, promoting agonist-induced vasodilation. Another important mechanism of influence may occur through positive feedback regulation of endothelial Ca<sup>2+</sup> signals, likely via amplification of influx through membrane cation channels. K<sub>Ca</sub>2.3 channels have recently been implicated in flow-mediated dilation of the arterial vasculature and may contribute to the crucial homeostatic role of shear stress in preventing vascular wall remodeling and progressive vascular disease (i.e., atherosclerosis). The impact of K<sub>Ca</sub>2.3 channels on endothelial Ca<sup>2+</sup> signaling under physiologically relevant shear stress conditions remains unknown. Methods: In the current study, we employ mice expressing an endothelium-specific Ca<sup>2+</sup> fluorophore (cdh5-GCaMP8) to characterize the K<sub>Ca</sub>2.3 channel influence on the dynamic Ca<sup>2+</sup> signaling profile along the arterial endothelium in the presence and absence of shear-stress. Results: Our data indicate K<sub>Ca</sub>2.3 channels have a minimal influence on basal Ca<sup>2+</sup> signaling in the carotid artery endothelium in the absence of flow, but they contribute substantially to amplification of Ca<sup>2+</sup> dynamics in the presence of flow and their influence can be augmented through exogenous positive modulation. Conclusions: The findings suggest a pivotal role for K<sub>Ca</sub>2.3 channels in adjusting the profile of homeostatic dynamic Ca<sup>2+</sup> signals along the arterial intima under flow. |
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| ISSN: | 2227-9059 |