Late Sodium Current of the Heart: Where Do We Stand and Where Are We Going?

Abstract

Late sodium current has long been linked to dysrhythmia and contractile malfunction in the heart. Despite the increasing body of accumulating information on the subject, our understanding of its role in normal or pathologic states is not complete. Even though the role of late sodium current in shaping action potential under physiologic circumstances is debated, it’s unquestioned role in arrhythmogenesis keeps it in the focus of research. Transgenic mouse models and isoform-specific pharmacological tools have proved useful in understanding the mechanism of late sodium current in health and disease. This review will outline the mechanism and function of cardiac late sodium current with special focus on the recent advances of the area.

Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal subunit regulation of the cardiac voltage-gated sodium channel

“…Another intriguing property of Na V 1.5 revealed here is that the inactivation kinetics of the α-subunit are accelerated by only β1. This property may be linked to forms of cardiac dysfunction that are accompanied by a persistent sodium current caused by altered inactivation kinetics ( 50 , 51 , 52 ). If so, altered association with β-subunits within a subpopulation of Na V 1.5 complexes might contribute to such a late current.…”

Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism

“…EADs are voltage oscillations during the phase 2 or 3 of the action potential caused by the reactivation of depolarizing currents. The increase of I Ca-L and the decrease of K + currents prolong AP duration and can induce EADs due to the activation of the late sodium current, I Na-L [ 25 ]. Our group has used the O’Hara-Rudy-dynamic model of ventricular AP [ 44 ] in in silico populations of control and hypothyroid patients and found higher incidence of EADs in the modeled hypothyroid patients [ 15 ].…”

Conductance Changes of Na+ Channels during the Late Na+ Current Flowing under Action Potential Voltage Clamp Conditions in Canine, Rabbit, and Guinea Pig Ventricular Myocytes

“…I Na,late contributes to the plateau phase of the ventricular action potential (AP) and is responsible for substantial Na + entry through sodium channels [9][10][11]. Augmentation of I Na,late leads to increased arrhythmia propensity associated with a longer action potential, increased heterogeneity of repolarization, and the development of afterdepolarizations [5,[12][13][14][15]. Consequently, selective inhibition of I Na,late has become a realistic therapeutical strategy [9,[16][17][18][19][20][21].…”