Table 2.
Model | Cell Type | INa, A/F | SSI | SSA | INaL | INa Kinetics | SCN5A mRNA | Nav1.5 Protein | Comments (References) |
---|---|---|---|---|---|---|---|---|---|
CaMKIIδc-OE | V | ↔ | ← | ↔ | ↑ | Slower recovery from inactivation and enhanced development of inactivation | ↑ | Trend to ↓ INa density; TG mice exhibit longer QRS intervals and monomorphic and polymorphic VT upon programmed electrical stimulation (126) | |
Muscle LIM protein MLP−/− | V | ↓ | ← | → | Slowed inactivation | ↓ | ↑ APD and EAD propensity, ↓ AP amplitude and rate of depolarization, lower Nav1.5 protein molecular weight (deglycosylation) (117) | ||
Unilateral nephrectomy/DOCA implantation, salt water substitution | V | ↓ | ↔ | ↔ | Reducing mitochondrial ROS by application of NAD+, mitoTEMPO, PKC inhibitors, or PKA activators, restored INa (58) | ||||
Inducible CX43-KO | LV, RV | ↓ | ↓ | Slower conduction and longer QRS in pacing induced VT+ mice (49) | |||||
PKP2 ± ARVC | V | ↓ | ← | ↔ | Slower recovery from inactivation | ↔ ICC | Abnormal ultrastructure; exaggerated INa decrease and slowed conduction w/flecainide, arrhythmia and SCD (19) | ||
ACE 8/8-OE | ↔ | ↔ ← | ← | Cardia-specific (α-MHC) overexpression; results in fourfold increase in ANG II (48, 52) | |||||
Calcineurin-OE | V | ↓↓ | ↔ | ↔ | ↔ | ↔ ICC | Hypertrophy, ↓ rate of AP rise, progressive heart block, SCD (39) | ||
Snail ± OE/DCM | V | ↓ | ↓ | DCM, ECG abnormalities, conduction defects; Homozygous mice lethal (44) | |||||
CSQ-OE | V | ↓↓ | → | → | DCM, hypertrophy, ↑ cell capacitance, ↑ PR and QT interval, conduction block (55) | ||||
Mdx (5cv) | V | ↓ | ↔ | ↓ | Dystrophin deficient; impaired conduction (35) | ||||
AnkB−/− KO | V | ↓ | ← | ← | ↑ | Slowed recovery from inactivation | Prolonged APD; impaired QT-rate adaptation; slowed HR; longer single Na channel mean open time; late single channel openings (23) |
ACE, angiotensin-converting enzyme; ANG II, angiotensin II; ARVC, arrhythmogenic RV cardiomyopathy; CSQ, calsequestrin; DCM, dilated cardiomyopathy; KO, knockout; MHC, myosin heavy chain; MLP, muscle LIM protein; OE, overexpression; PKP2, plakophilin-2; TG, transgenic; VT, ventricular tachycardia.