Table 2.
Experimentally obtained properties related to specific levels of cardiomyocyte function that can affect contractility or cellular effects of compounds. The values of properties have been published and are presented for primary cardiomyocytes, hiPSC-cardiomyocytes in 2D, and engineered heart tissues. I generally represents the current density of different regulators of electrophysiological function: sodium-calcium exchange current (INCX), sodium current (INa), rapidly activating component of the rectifier potassium current (IKr), L-type calcium current (ICa,L), inward rectifier potassium current (IK1), “funny” current (If), slowly activating component of the delayed rectifier potassium current (IKS), calcium-insensitive transient outward current (Ito1), and T-type calcium current (ICa,T). MHC represents myosin-heavy chain, which affects the physiological relevance of contractility.
| Functional property | Primary cardiomyocytes | hiPSC-cardiomyocytes in 2D | Engineered heart tissues |
|---|---|---|---|
| Membrane capacitance (pF) | ∼ 200pF (Feric and Radisic, 2016) | ∼ 10–55 (Feric and Radisic, 2016; Vaidyanathan et al., 2016) | ∼ 28.2–47 isolated cells (Horvath et al., 2018) |
| Maximal upstroke velocity (V/s) | ∼ 230–253 (Lemoine et al., 2017) | ∼ 13.1–146.5 (Lemoine et al., 2017) | ∼ 219 (Lemoine et al., 2017) |
| Action potential duration (ms) | ∼ 228–411(Feric and Radisic, 2016; Horvath et al., 2018) | ∼ 200–500 (Feric and Radisic, 2016) | ∼ 206–422 (Horvath et al., 2018) |
| Action potential amplitude (mV) | ∼ 94.3–104.8 (Lemoine et al., 2017) | ∼ 88.1–116 (Lemoine et al., 2017) | ∼ 102.7(Lemoine et al., 2017) |
| Resting membrane potential (mV) | ∼ -72.6−90 (Feric and Radisic, 2016; Lemoine et al., 2017) | ∼ -37−70.5 (Feric and Radisic, 2016; Lemoine et al., 2017) | ∼ -73.5(Lemoine et al., 2017) |
| I NCX (pA/pF) | ∼ -1.0 (Koivumaki et al., 2018) | ∼ -1.2−6.9 (Barbuti et al., 2016) | Expression levels of NCX-like 2D (Mannhardt et al., 2016) |
| INa (pA/pF) | ∼ -20.2–−14.3 (Lemoine et al., 2017) | ∼ -10.3 (Lemoine et al., 2017) | ∼ -18.5(Lemoine et al., 2017) |
| I Kr (pA/pF) | ∼ 0.25–0.6 (Casini et al., 2017) | ∼ 0.18–2.5 (Casini et al., 2017) | Magnitude reported ∼ 1/3 < primary tissue (Lemoine et al., 2018) |
| I Ca,L (pA/pF) | ∼ -3.8–10.2 (Casini et al., 2017) | ∼ -6.6–58 (Casini et al., 2017) | Magnitude reported 1.5× > 2D (Uzun et al., 2016) |
| I K1 (pA/pF) | ∼ -3.6–32.1 (Casini et al., 2017) | ∼ -0.8–5.1 (Casini et al., 2017) | 1/2 magnitude recorded with 2D (Horvath et al., 2018) |
| I f (pA/pF) | ∼ -1.18 (Casini et al., 2017) | ∼ -0.9–4.1 (Casini et al., 2017) | Magnitude reported to be 5× > primary tissWue (Lemoine et al., 2018) |
| I KS (pA/pF) | ∼ 0.18 (Casini et al., 2017) | ∼ 0.22–2.9 (Casini et al., 2017) | Magnitude reported to match primary tissue (Lemoine et al., 2018) |
| I to1 (pA/pF) | ∼ 4.4–10.6 (Casini et al., 2017) | ∼ 1.3–1.9 (Casini et al., 2017) | – |
| I Ca,T (pA/pF) | Expressed in immature cells and pacemaker cells (Mesirca et al., 2014) | ∼ -2.1 ± 0.8 (Zhao et al., 2018) | Magnitude like 2D (Uzun et al., 2016) |
| Relative expression of α- adrenoceptor 1A | ∼ 100 (Földes et al., 2014) | Absent (Földes et al., 2014) | – |
| Relative expression of α- adrenoceptor 1B | ∼ 10,000 (Földes et al., 2014) | ∼ 100–1,000 (Földes et al., 2014) | – |
| Relative expression of β1-adrenoceptors | ∼ 5,000 (Jung et al., 2016) | Residual to ∼ 3,000 (Jung et al., 2016) | Improved β-adrenergic response relative to 2D (Weinberger et al., 2017) |
| Relative expression of β2- adrenoceptors | ∼ 5,000 (Jung et al., 2016) | ∼ 2,500–9,000 (Jung et al., 2016) | Improved β-adrenergic response relative to 2D (Weinberger et al., 2017) |
| Relative expression of β3- adrenoceptors | ∼ 1,000 (Jung et al., 2016) | Residual-∼ 500 (Jung et al., 2016) | Improved β-adrenergic response relative to 2D (Weinberger et al., 2017) |
| Cell shape and size | Tubular, long, and narrow (length: 50–100 µm, diameter: 10–25 µm) (Opie, 2004a) | Circular (variable area: 1,000–1,800 µm2) (Lewandowski et al., 2018) | Tubular, long, and narrow, but not as large as primary cells (Weinberger et al., 2017) |
| Organization of mitochondria | Distributed proximally to myofibrils, occupy ∼ 20 to 40% of cell (Yang et al., 2014) | Irregular cytoplasmic distribution, less dense than in primary cells (Yang et al., 2014) | Systematically present, but with immature organization (Mannhardt et al., 2016) |
| Relative expression of Connexin-43 expression | ∼ 3.2 (Lewandowski et al., 2018) | ∼ 1 (Lewandowski et al., 2018) | Increased when exposed to chronic electrical stimulation (Chiu et al., 2011) |
| Connexin-43 localization | Polarized to intercalated discs (Stroemlund et al., 2015) | Intracellular localization and homogeneous distribution along the cell–cell interface (Seki et al., 2014) | No differences between end-to-end and lateral cell–cell contacts (Lemoine et al., 2017) |
| Titin isoforms | N2B > N2BA (Yang et al., 2014) | N2BA > N2B (Yang et al., 2014) | No reported data. Capable of detecting effects caused by titin mutations (Hinson et al., 2015) |
| α-MHC/β-MHC | < < 1 (Yang et al., 2014) | < 1 (Yang et al., 2014) | < Than 2D (Schaaf et al., 2011) |
| T-tubules | Highly abundant and homogeneously localized in proximity to Z-lines (Mitcheson et al., 1998) | Absent (Veerman et al., 2015) | Reported in one study (Ronaldson-Bouchard et al., 2018) |