Extracellular ATP regulates glomerular endothelial cell function

Area of Science:

• Cell biology
• Renal physiology
• Molecular pharmacology

Background:

• Glomerular endothelial cells (GECs) are crucial components of the renal filtration barrier.
• GECs play a role in glomerular pathophysiological processes.
• Recent advancements have enabled the culture of GECs, facilitating experimental investigation.

Purpose of the Study:

• To investigate the effects of extracellular adenosine triphosphate (ATP) on GEC membrane potential and intracellular calcium activity.
• To elucidate the purinergic receptor subtypes involved in ATP signaling in GECs.

Main Methods:

• Patch clamp technique in the fast whole-cell configuration was used to measure membrane voltage.
• Fura-2 imaging was employed to quantify intracellular calcium activity ([Ca2+]i) in single GECs.
• Various purine nucleotides were tested to determine their potency in stimulating [Ca2+]i and inositol phosphate formation.

Main Results:

• GECs exhibit a stable resting membrane potential of -88 mV.
• ATP induced a transient hyperpolarization followed by a sustained depolarization, inhibited by flufenamate.
• ATP stimulated a biphasic increase in [Ca2+]i, with an extracellular calcium-dependent plateau phase.

Conclusions:

• Extracellular ATP modulates membrane voltage and intracellular calcium levels in cultured GECs.
• The P2y2 receptor is identified as the primary mediator of ATP's effects on GEC membrane voltage and [Ca2+]i.
• These findings contribute to understanding the role of purinergic signaling in glomerular endothelial cell function.