Calcium Oscillations Within Juxtaglomerular Cell Clusters Control Renin Release

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Cellular Signaling

Background:

• Juxtaglomerular cells regulate blood pressure and fluid balance.
• They secrete renin in response to low blood pressure, initiating the renin-angiotensin system.
• Angiotensin II (Ang II) normally inhibits renin release via intracellular calcium (Ca2+).

Purpose of the Study:

• To investigate the dynamics and sources of intracellular Ca2+ signaling in juxtaglomerular cells.
• To understand how these Ca2+ signals are organized within juxtaglomerular cell clusters.
• To link Ca2+ signaling patterns to renin secretion regulation.

Main Methods:

• Generated mice with juxtaglomerular cell-specific Ca2+ indicator (GCaMP6f).
• Performed ex vivo Ca2+ imaging in perfused kidney slices and in vivo imaging in native kidneys.
• Used Ang II, Ca2+ channel inhibitors, and losartan; measured renin secretion via ELISA.

Main Results:

• Ang II stimulation induced coordinated, propagating intracellular Ca2+ oscillations in juxtaglomerular cell clusters.
• These oscillations involved endoplasmic reticulum Ca2+ release, ORAI channels, and gap junctions.
• In vivo and ex vivo imaging showed similar Ca2+ oscillation patterns, which inversely correlated with renin secretion.

Conclusions:

• Angiotensin II triggers coordinated intracellular and intercellular Ca2+ oscillations in juxtaglomerular cells.
• These signals are mediated by ER Ca2+ release, ORAI channels, and gap junctions.
• These Ca2+ oscillations suppress renin secretion, contributing to blood pressure homeostasis.