What is the role of the Epithelial Sodium Channel (ENaC) in kidney physiology?

From the Guidelines

The Epithelial Sodium Channel (ENaC) plays a critical role in kidney physiology by regulating sodium reabsorption in the distal nephron and collecting duct, and its dysfunction can lead to various conditions such as hypertension or salt-wasting disorders. ENaC is located on the apical membrane of epithelial cells and allows sodium to enter from the tubular lumen into the cell, which is then transported out via the Na⁺/K⁺-ATPase pump on the basolateral membrane. The activity of ENaC is primarily regulated by aldosterone, which increases channel expression and activity, thereby enhancing sodium reabsorption and consequently water retention 1. This mechanism is essential for maintaining blood pressure and electrolyte balance.

Some key points about ENaC in kidney physiology include:

• ENaC is the target of potassium-sparing diuretics like amiloride, which blocks these channels to promote sodium excretion while conserving potassium 1
• Amiloride has been shown to lower blood pressure in patients with resistant hypertension by antagonizing the epithelial sodium channel in the distal collecting duct of the kidney 1
• The use of amiloride or other ENaC blockers can have significant implications for patients with conditions like Liddle syndrome or pseudohypoaldosteronism type 1, where ENaC activity is altered 1
• Understanding ENaC function is fundamental for comprehending kidney electrolyte handling and the pathophysiology of various hypertensive and salt-wasting disorders.

In terms of clinical implications, the regulation of ENaC activity is crucial for maintaining proper blood pressure and electrolyte balance, and dysfunction of this channel can have significant consequences. As such, it is essential to consider the role of ENaC in kidney physiology when managing patients with conditions related to sodium reabsorption and blood pressure regulation.

From the Research

Role of ENaC in Kidney Physiology

• The Epithelial Sodium Channel (ENaC) plays a crucial role in sodium reabsorption in the distal part of the renal tubule, with its activity regulated by aldosterone and hormones involved in maintaining sodium balance, blood volume, and blood pressure 2.
• ENaC is rate-limiting for Na(+) absorption in the aldosterone-sensitive distal nephron, comprising the late distal convoluted tubule, the connecting tubule, and the entire collecting duct 3.
• The channel's function and regulation are essential for maintaining sodium balance and blood pressure control, with dysregulation leading to conditions such as Liddle syndrome, a severe form of salt-sensitive hypertension 3, 4.
• ENaC modulators can be used to control channel activity, which is important for electrolyte and extracellular volume homeostasis, and thus blood pressure regulation 5.
• Recent studies have also found that ENaC expressed in other cells, including immune cells, can influence blood pressure via extra-renal mechanisms, highlighting the channel's role in salt-sensitive hypertension beyond the kidney 6.

ENaC Regulation and Function

• ENaC activity is enhanced by the steroid hormone aldosterone, which is a key regulator of channel function 2, 5.
• The channel's expression and activity can be influenced by various factors, including genetic mutations, salt intake, and single-nucleotide polymorphisms (SNPs) 3, 4.
• ENaC's role in the kidney is well established, but its expression and function in other tissues, such as vascular smooth muscles, endothelial cells, and immune cells, are also important for blood pressure regulation 6.