ENaC and Blood Pressure – Experimental Evidence Review

These flashcards cover key concepts related to ENaC and its impact on blood pressure regulation, focusing on experimental findings and clinical implications.

What is the role of ENaC in blood pressure regulation?

ENaC regulates sodium reabsorption in the kidney, impacting blood pressure.

What happens to blood pressure when mutations occur in the ENaC subunits?

Mutations in ENaC subunits can lead to dysregulation of blood pressure.

What key experimental finding was associated with Liddle's Syndrome?

Mutant ENaC displays a 2-3 times increase in amiloride-sensitive current compared to wild type.

What does the PY motif in β-ENaC interact with, and what happens when it is mutated?

The PY motif binds Nedd4-2; when mutated, the channels do not bind Nedd4-2, leading to increased channel activity and hypertension.

What is the significance of the T594M variant in β-ENaC?

The T594M variant results in loss of PKC phosphorylation site and enhanced channel activity.

How does the V481M variant alter ENaC function?

The V481M variant leads to increased open probability and reduced Na⁺ self-inhibition.

What characterizes the mutations leading to Pseudohypoaldosteronism Type I?

Loss-of-function mutations in α, β, or γ ENaC subunits are characterized, resulting in no detectable current.

How does nephrotic syndrome affect ENaC activity?

Nephrotic syndrome leads to post-translational activation of ENaC through plasmin cleavage.

What is the role of SGK1 in regulating ENaC activity?

SGK1 phosphorylates Nedd4-2, leading to increased ENaC current.

How do epigenetic mechanisms regulate ENaC expression?

Dot1a and Af9 bind to the αENaC promoter; their knockdown increases αENaC expression.

What was the conclusion of the GenSalt Study related to ENaC and blood pressure?

V481M carriers showed increased blood pressure sensitivity to high sodium intake, validating the functional link.

What therapeutic approach is supported by the evidence of ENaC mutations?

Amiloride is shown to effectively normalize blood pressure in patients with Liddle's Syndrome.