Table 1.
Sequence homology in ion channels between human, hiPSC CMs and animal models
| Humana,1,2 | Sheepb | Mouse | Zebrafishc | hiPSC CMs | ||||
|---|---|---|---|---|---|---|---|---|
| Ion Current | Protein (Accession number) | * | Seq. homology to human (Accession no.) | * | Protein; Seq. homology to human (Accession no.) | * | Protein; Seq. homology to human (Accession no.) | * |
| ICaL | Cav1.2 (NP_955630.3) | ✓ 3 | 92% (XP_027823851.1) | ✓ 4 | Cav1.2 91% (NP_033911.2) | ✓ 5 | Cav1.2 76% (NP_571975.1) | ✓ 6,7 |
| IKr | Kv11.1 (BAA37096.1) | ✓ 8 | 95% (XP_027824801.1) | – 9,10 | Kv11.1 96% (NP_038597.2) but proscribed for repolarization assays in ICH S7B guidelines.10 | ✓ 5,11 |
Kv11.2d 60% (NP_998002.1) 99% (canonical binding site) |
✓ 6,7 |
| IKs | Kv7.1 (NP_000209.2) | ✓ 8 | 89% (XP_027815648.1) | – 9,10 | Kv7.1 88% (NP_032460.2) but proscribed for repolarization assays in ICH S7B guidelines.10 | ✓ 12 | Kv7.1 67% (NP_001116714.1) | ✓ 6,7 |
| Ito | ||||||||
|
Ito (slow) Ito (fast) Ito (fast) |
Kv1.4 (NP_002224.1) Kv4.2 (NP_036413.1) Kv4.3 (NP_004971.2) |
✓ 13 |
95% (XP_027835381.1) 99% (XP_011993623.1) 99% (XP_011990111.1) |
✓ 9,14 |
Kv1.4 97% (NP_067250.2) Kv4.2 99% (NP_062671.1) Kv4.3 99% (NP_064315.1) |
– 15,16 |
Kv1.4 63% (XP_005169005.1) zShal2 d 80% (NP_001076336.1) zShal3 d 75% (NP_956096.1) |
✓ 6,7 |
| IK1 |
Kir2.1 (NP_000882.1) Kir2.3 (NP_690607.1) |
✓ 17 |
99% (XP_027829809.1) 98% (XP_004023700.2) |
✓ 18 |
Kir2.1 98% (NP_032451.1) Kir2.3 98% (NP_032453.3) |
✓ 1,2,5 |
Kir2.4 d 67% (NP_001313403.1) Kir2.4 d 61% (NP_001313403.1) |
– 6,7 |
hiPSC CMs, human induced pluripotent stem cell derived cardiomyocytes; * column indicating whether the human ionic current is present in the model organism: ✓ present; – negligible/not present. Numbers in brackets indicate relevant reference. Sequence homologies to humans are given in %.
aIon channel isoforms most expressed in human heart. bNo protein name since REFSEQ is predicted by automated computational analysis. cChannel isoforms most expressed in zebrafish heart and their sequence homology to corresponding human channel isoforms. dIsoforms that are differentially expressed compared to humans.
1(Vornanen & Hassinen, 2016) 2(Vornanen et al., 2018) 3(Dibb et al., 2004) 4(Moosmang et al., 2005) 5(Nemtsas et al., 2010) 6(Ma et al., 2011) 7(Fermini et al., 2016) 8(Noble & Tsien, 1969) 9(Huang, 2017) 10(European Medicines Agency, 2005) 11(Warren et al., 2017) 12(Abramochkin et al., 2018) 13(Boyett, 1981) 14(Bovo et al., 2013) 15(Alday et al., 2014) 16(Nakamura & Coetzee, 2008) 17(Weidmann, 1955) 18(Lopatin & Nichols, 2001)