Persistent sodium current (INaP) (INaP)

Persistent sodium current (INaP) is a small, non-inactivating component of the total sodium conductance that remains active long after the initial peak sodium current has inactivated during an action potential [Stafstrom, 2007]. It is mediated by various isoforms of voltage-gated sodium channels (Nav), including Nav1.1, Nav1.2, and Nav1.6 in the central nervous system and Nav1.5 in the myocardium, where it is often termed the "late" sodium current [Saint, 2008; George, 2005]. Biologically, INaP is crucial for regulating neuronal excitability, lowering the threshold for action potential firing, and facilitating repetitive firing and subthreshold oscillations [Stafstrom, 2007]. In pathological states, such as ischemia, nerve injury, or genetic mutations (e.g., SCN5A mutations in Long QT Syndrome type 3), INaP is significantly enhanced, leading to cellular hyperexcitability, calcium overload, and subsequent tissue damage or arrhythmias [Saint, 2008; Beltran-Alvarez et al., 2014]. Pharmacological inhibition of INaP is a validated therapeutic strategy; drugs like riluzole and ranolazine selectively target this persistent component to treat amyotrophic lateral sclerosis and chronic angina, respectively, without disrupting the peak sodium current necessary for normal cellular signaling [Stafstrom, 2007; Mantegazza et al., 2010].

Other names

Late sodium currentINa,lateNon-inactivating sodium currentSlowly inactivating sodium currentPersistent Na+ current

Selective inhibition of the persistent or late component of voltage-gated sodium channel conductance, reducing sustained sodium influx during the action potential plateau or at subthreshold voltages [Stafstrom, 2007; Saint, 2008].