Table 1.

I_Na changes in heart disease

Model	Species	Cell Type	INa, A/F	SSI	SSA	INaL	INa Kinetics	SCN5A mRNA	Nav1.5 Protein	Comments (References)
HCM	Human	V				↑		↔	↔	Mild to moderate HF, NYHA class II–III (29)
CM/CHD ± HF	Human	V		↔	↔		Development and recovery from inactivation ↔			Window current detected, no Δ in HF (102)
Explanted HF	Human	LV						↔		Myocytes from midmyocardial wall (50)
Explanted HF	Human	LV, RV						↑		(91)
Explanted end-stage HF	Human	LV, RV						↓		No Δ with LVADs; CaMKIIγ and δ ↔ in HF LVs; CaMKIIδ ↑ twofold in RV; CaMKIIδ ↓ to 40% of controls with LVAD (17)
Explanted HF	Human	V						↑Truncation ↓native		↓ protein expression and current in heterologous system with truncation variants (108)
Arrhythmogenic cardiomyopathy	Human	LV, RV							↓ ICC	(87)
Explanted/pacing	Human/dog	V	↓	↔	↔	↑		↔		No Δ in Nav 1.1, 1.3, β1- and β2-subunits; ↑ cell capacitance in HF (119)
Explanted/pacing	Human/dog	V				↑	Slower INaL decay			(69, 70)
Multiple coronary microembolizations	Dog	LV	↓	↔	↔	↑		↔	↓	↓ Peak reversed by carvedilol; no Δ in β1 mRNA, β1 or β2 protein; ranolazine decreased APD, EADs, APD beat-to-beat variability and dispersion (68, 118)
Pacing-induced HF	Dog	V	↔	↔			Rate and voltage dependence of INa decay ↔			Ito downregulation explains APD prolongation (51)
Ventricular tachypacing	Dog	P						↓	↓	Slowed conduction and AP rate of rise (64)
5-day infarction/ischemia	Dog	EBZ	↓↓	←	↔←		Slower recovery from inactivation and enhanced development of inactivation		Abnormal Nav1.5 cell surface staining	Reentrant excitation; ventricular tachycardia; slowed AP rate of rise (9, 10, 97)
Pressure/volume overload	Rabbit	V	↔		↔					↑Heart weight, longer QRS duration, slower conduction velocity (131)
Aortic banding	Guinea pig	LV	↑	↔	↔		Time course of INa inactivation and recovery ↔			Increase in INa density with cardiac hypertrophy (at 4 wk) is attenuated with progression to cardiac failure (at 8 wk) (3)
Post-MI	Rat	LV					Slower decay	↔		18% TTX-sensitive component of APD prolongation; ↑Nav1.1 mRNA and protein expression (45)
Siderotic heart disease	Gerbil/neonatal rat	V	↓	←	↔		Time course of INa activation and inactivation ↔; slower recovery from inactivation		↔	↔Single channel currents, ↓AP overshoot and duration (57)
RV pressure overload	Rat	LV, RV	↔		↑RV			↔		CTEPH model; reduced CX43; trend to INa density ↓ in both LV and RV (42)
Volume overload	Rat	SAN						↓	↓	Nav1.1 and Nav1.6 primary isoforms, Nav1.5 and Nav1.7 weakly expressed, Nav1.2 and Nav1.3 not expressed; ↓ HR and ↑ sinus node recovery time (32)

APD, action potential (AP) duration; CM, cardiomyopathy; CHD, congenital heart disease; CTEPH, chronic thromboembolic pulmonary hypertension; CX43, connexin 43; EADs, early afterdepolarizations; EBZ, epicardial border zone; HCM, hypertrophic cardiomyopathy; HF, heart failure; HR, heart rate; ICC, immunocytochemistry; I_Na, Na current; I_Na,L, late I_Na; I_to, transient outward K current; LV, left ventricle; LVAD, LV assist device; MI, myocardial infarction; Na_V1.5, voltage-gated Na channel isoform 1.5; NYHA, New York Heart Association; P, Purkinje; RV, right ventricle; SAN, sinoatrial node; SSA, steady-state activation; SSI, steady-state inactivation; TTX, tetrodotoxin; V, ventricle.