Abstract
Cardiac myocyte contraction is initiated by a set of intricately orchestrated electrical impulses, collectively known as action potentials (APs). Voltage-gated sodium channels (NaVs) are responsible for the upstroke and propagation of APs in excitable cells, including cardiomyocytes. NaVs consist of a single, pore-forming α subunit and two different β subunits. The β subunits are multifunctional cell adhesion molecules and channel modulators that have cell type and subcellular domain specific functional effects. Variants in SCN1B, the gene encoding the Nav-β1 and -β1B subunits, are linked to atrial and ventricular arrhythmias, e.g., Brugada syndrome, as well as to the early infantile epileptic encephalopathy Dravet syndrome, all of which put patients at risk for sudden death. Evidence over the past two decades has demonstrated that Nav-β1/β1B subunits play critical roles in cardiac myocyte physiology, in which they regulate tetrodotoxin-resistant and -sensitive sodium currents, potassium currents, and calcium handling, and that Nav-β1/β1B subunit dysfunction generates substrates for arrhythmias. This review will highlight the role of Nav-β1/β1B subunits in cardiac physiology and pathophysiology.
Highlights
The heart contracts to pump blood throughout the body. It consists of specialized cells called cardiac myocytes (CMs), and contraction of CMs is initiated by electrical impulses called action potentials (APs) (Nerbonne and Kass, 2005)
Nav1.5 channels cluster at cell–cell junction sites at the intercalated disk (ID), where they co-localize with the cardiac gap junction (GJ) protein, connexin-43 (Cx43) (Maier et al, 2002, 2004) (Figure 3B)
It is intriguing to consider that NaV-β1 may serve as a central communication hub between sodium, potassium, and calcium channel families to coordinate depolarization, repolarization, and calcium signaling in CMs
Summary
The heart contracts to pump blood throughout the body It consists of specialized cells called cardiac myocytes (CMs), and contraction of CMs is initiated by electrical impulses called action potentials (APs) (Nerbonne and Kass, 2005). Voltage-gated sodium channels (NaVs) activate and inactivate rapidly to allow sodium influx (Hille and Catterall, 2012). This is responsible for the rising phase and propagation of the AP in mammalian CMs (Nerbonne and Kass, 2005). NaV-β subunits are expressed in mammalian heart (Isom et al, 1992; Makita et al, 1994) and their functional loss can result in electrical abnormalities that predispose patients to arrhythmias. We will focus our review on the current understanding of NaV-β1/β1B function in CMs and discuss disease implications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
