Calcium Signal Profiles in Vascular Endothelium from Cdh5-GCaMP8 and Cx40-GCaMP2 Mice

Area of Science:

• Vascular biology
• Calcium signaling
• Genetically encoded calcium indicators

Background:

• Endothelial calcium signals are crucial for vascular function.
• Previous Cx40-GCaMP2 mouse models had limitations in dynamic range and venous endothelium signal detection.
• Newer GCaMP variants (GCaMP5/6/7/8) show promise but their endothelial performance is unknown.

Purpose of the Study:

• To characterize a novel Cdh5-GCaMP8 mouse line for endothelial calcium imaging.
• To compare the performance of Cdh5-GCaMP8 mice with Cx40-GCaMP2 mice.
• To investigate endothelial calcium signals in mesenteric arteries and veins.

Main Methods:

• Developed and characterized a mouse line expressing GCaMP8 under the VE-cadherin (Cdh5) promoter.
• Recorded endothelial calcium signals in mesenteric arteries and veins using Cdh5-GCaMP8 and Cx40-GCaMP2 mice.
• Investigated calcium signals mediated by IP3 receptors and TRPV4 channels.

Main Results:

• Cdh5-GCaMP8 mice exhibited lower baseline fluorescence, higher dynamic range, and greater signal amplitudes than Cx40-GCaMP2 mice.
• Enabled first-time recordings of discrete calcium signals in the intact venous endothelium.
• Revealed significant differences in IP3 receptor and TRPV4 channel activity between arteries and veins.

Conclusions:

• Cdh5-GCaMP8 mice offer enhanced dynamic range and sensitivity for low-intensity signals.
• This model allows for calcium signal recordings in the venous endothelium, a previous limitation.
• Provides new insights into regional differences in endothelial calcium signaling.