Table 2.
Murine models involving sinoatrial pacemaker function
| Gene | Genotype | Phenotype | Reference Nos. |
|---|---|---|---|
| Rapid K+ current IKr | |||
| Erg1b | Erg1b−/− | Loss of IKr; bradycardic episodes | 210, 626 |
| Hyperpolarization-activated cyclic nucleotide-gated (HCN) current If | |||
| Hcn1 | Hcn1−/− (global) | Bradycardic, reduced If | 310, 837 |
| Hcn2 | Hcn2−/− (global) | Sinus dysrhythmia and reduced If | 699 |
| Hcn2−/− (cardiac-specific) | Sinus dysrhythmia | 311 | |
| Hcn3 | Hcn3−/− (global) | Sinus rhythm, normal If | 311 |
| Hcn4 | Hcn4−/− (global) | Embryologically lethal | 1094 |
| Hcn4−/− (cardiac-specific) | Embryologically lethal; bradycardia; reduced If | 1094 | |
| Hcn4-R669Q/R669Q (global) | Embryologically lethal; bradycardia; slowed If | 410 | |
| Hcn4−/− (global; inducible) | Sinus pauses; reduced If | 426 | |
| KiT-Hcn4−/− (inducible) | Sinus pauses; reduced If | 435 | |
| Ci-Hcn4−/− (inducible, cardiac-specific) | Bradycardia; reduced If | 74 | |
| Hcn4–573X KI (inducible, cardiac-specific) | Bradycardia; normal If | 20, 425 | |
| Voltage-gated Ca2+ current ICa | |||
| Cacna1d | Cacna1d−/− | Bradycardia; 70% reduced ICa,L; residual ICa,L due to Cav1.2 | 720, 751, 1344 |
| Cacna1c | Cacna1c-DHP−/− | Dihydropyridine-insensitive Cav1.2, continued DHP effects implicating Cav1.3 | 1066 |
| Cacna1g | Cacna1g−/− | ICaT due to Cav3.1 entirely lacking; slowed atrioventricular conduction; moderate bradycardia | 724 |
| Cacna1h | Cacna1h−/− | Normal ECG characteristics | 186 |
Note: mutations involving Scn5a+/− (Scn5a) are covered in Table 4.