Table 1.
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; INa, Na current; INa,L, late INa; Ito, transient outward K current; LV, left ventricle; LVAD, LV assist device; MI, myocardial infarction; NaV1.5, 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.