Sodium Channel Structure and Function

Introduction to Sodium Channels

• The American Heart Association suggests that β-subunits alter voltage dependence of both activation and inactivation, change sarcolemmal expression levels, and contribute to interactions with the extracellular matrix in patients with cardiac conditions 1, 2

Clinical Implications

• The American College of Cardiology recommends that mutations affecting fast inactivation can prolong sodium current during phase 0, leading to conditions like long QT syndrome type 3, where delayed inactivation causes persistent inward sodium current 3

Regulation and Modulation of Sodium Channels

• The American Heart Association notes that ion channels exist as part of extensive macromolecular complexes that allow rapid modulation in response to extrinsic factors, and channel regulation occurs on multiple temporal and spatial scales 4, 5
• The American Heart Association also states that novel long-QT syndrome and Brugada syndrome susceptibility genes involve channel-interacting proteins, including caveolin-3, sodium channel β-subunit, yotiao, and glycerol-3-phosphate dehydrogenase 1-like protein 4