Voltage-gated sodium (NaV) channels are responsible for the rapid rising-phase of action
potentials in excitable cells. Over 1,000 mutations in NaV channels are associated with …

Late I Na is an integral part of the sodium current, which persists long after the fast-
inactivating component. The magnitude of the late I Na is relatively small in all species and …

Voltage-gated sodium channel Na v 1.5 generates cardiac action potentials and initiates the
heartbeat. Here, we report structures of Na V 1.5 at 3.2–3.5 Å resolution. Na V 1.5 is …

Abstract Nav1. 5, the primary voltage‐gated Na+ (Nav) channel in heart, is a major target for
class I antiarrhythmic agents. Here we present the cryo‐EM structure of full‐length human …

Rationale: The class Ic antiarrhythmic drug flecainide prevents ventricular tachyarrhythmia in
patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease …

Potency of drug action is usually determined by binding to a specific receptor site on target
proteins. In contrast to this conventional paradigm, we show here that potency of local …

Cardiomyocytes (CMs) differentiated from patient-specific induced pluripotent stem cells
(iPSCs [iPSC-CMs]) have now been shown to provide valuable models of heritable cardiac …

A long-sought, and thus far elusive, goal has been to develop drugs to manage diseases of
excitability. One such disease that affects millions each year is cardiac arrhythmia, which …

The human voltage-gated sodium channel, hNaV1. 5, is responsible for the rapid upstroke of
the cardiac action potential and is target for antiarrhythmic therapy. Despite the clinical …

Local anesthetic drugs interfere with excitation and conduction by action potentials in the
nervous system and in the heart by blockade of the voltage-gated Na channel. Drug affinity …