Table 2 Comparison of INa properties in isolated human induced pluripotent stem cell-derived and adult cardiomyocytes. HiPSC-CM: human induced pluripotent stem cell-derived cardiomyocyte; ML: monolayer; EHT: engineered heart tissue; V0.5: voltage of half-maximal (in)activation; k: slope factor of voltage-dependence of (in)activation; *overlap-potential (Vm) was calculated: ((kact*V0.5Inact)−(−kInact*V0.5act))/(kInact+kact) (details in supplementary data); #availability at overlap (%) was calculated = 1/(1+EXP((−V0.5Inact+overlap-potential)/kInact ))*100; INa ext: sodium concentration of the extracellular (bath) solution, INa int: sodium concentration of the intracellular (pipette) solution; MDP: maximum diastolic potential; RMP: resting membrane potential (=take-off potential); dV/dtmax: maximum upstroke velocity; APA: action potential amplitude.
CM-type | ML hiPSC | EHT hiPSC | ventri-cular | ventri-cular | atrial | atrial | atrial | atrial | atrial | atrial | atrial | ML hiPSC(on Matri-gel) | Single hiPSC (on Matri-gel) | ML hiPSC | ML hiPSC | ML hiPSC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Capacitance (pF) | 24.1 | 27.9 | 194 | 126 | 73.1 | 72.1 | 66 | 89 | 17.0 | 42 | 15.8 | |||||
Peak INa density (pA/pF) | −10.3 | −18.5 | −20.2 | −17.8 | −14 | −30 | −50.2 | −37 | −30.0 | −160 | −105 | ~−68 | −118 | −264.4 | −216.7 | |
V0.5 activation (mV) | −34.6 | −36.2 | −42.8 | −38.9 | −38.8 | −50.2 | −38.6 | ~−44 | −42.4 | −42 | −34.1 | |||||
kact | 5.8 | 5.9 | 6.0 | 6.5 | 5.3 | 7.2 | 1.8 | 5.9 | ||||||||
V0.5 inactivation (mV) | −89.8 | −91.3 | −97.3 | −95.8 | −97.1 | −97.2 | −95.1 | −72.2 | −77 | −88.0 | −82.8 | −61.4 | −72.1 | |||
kinact | 6.1 | 7 | 5.8 | 5.3 | 6.2 | 7.4 | 4.9 | 7.6 | 5.7 | |||||||
∆V0.5(Act-Inact) (mV) | 55.2 | 55.1 | 54.5 | 56.9 | 58.3 | 47.0 | 56.5 | ~44 | 19.0 | 38.0 | ||||||
Overlap-potential (mV)* | −61.5 | −61.4 | −70.5 | −70.2 | −71.9 | −66.5 | ~−61 | −46.0 | −53.4 | |||||||
Overlap-availability (%)# | 0.9 | 1.4 | 1.0 | 0.8 | 1.7 | 2.0 | ~4 | 11.7 | 3.6 | |||||||
Days after differentiation | 28 | 28 | 4–7 | 5–7 | 28 | 18 | 16 | |||||||||
INa ext (mmol/L) | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 10 | 120 | 150 | 20 | 10 | 135 | 130 | 50 | |
INa int (mmol/L) | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 10 | 70 | 10 | 5 | 5 | 5 | 5 | 10 | |
Holding potential (mV) | −110 | −110 | −140 | −140 | −120 | −110 | −140 | −140 | −135 | −120 | −140 | −120 | −90 | −90 | −80 | |
Temperature (°C) for INa | 21 | 21 | 17 | 17 | 23 | 21 | 22 | 22 | 24 | 21 | 37 | 22 | 24 | 36 | 36 | |
Pulse frequency (Hz) | 0.5 | 0.5 | 0.1 | 0.1 | 0.1 | 0.5 | 0.1 | 0.5 | 0.2 | |||||||
IC50 TTX (µmol/L) | 1.4 | 1.7 | 1.1 | 10.6 | 0.6 | |||||||||||
Temperature (°C) for AP | 37 | 37 | 37 | 37 | 22 | 22 | 24 | 21 | 37 | 22 | 24 | 36 | 36 | |||
MDP (mV) | −78.4 | −74.8 | −72.6 | −77.5 | 74.0 | −60.9 | −72.4 | −75.6 | ||||||||
RMP (=take-off) (mV) | −73.5 | −74.8 | −72.6 | −70.5 | ||||||||||||
dV/dtmax (V/s) | 219 | 253 | 230 | 146.5 | 84 | 13.1 | 115.7 | 27.8 | ||||||||
APA (mV) | 102.7 | 104.8 | 94.3 | 116 | 124 | 88.1 | 106.0 | 104.0 | ||||||||
Author/year | This study | This study | This study | Sakak-ibara et al. 199317, Am J Physiol | Sakak-ibara et al. 199216, Circ Res | Li et al. 2009, Cardi-ovasc Res | Wettwer et al. 20137, Cardi-ovasc Res | Bosch et al. 1999, Cardi-ovasc Res | Feng et al. 199621, Am J Physiol | Schneider et al. 1994, Pflügers Arch Eur J Physiol | Busta-mante et al. 1983, Science | Herron et al. 201612, Circ Arrhy-thmia Elect-roph | Feaster et al. 201511, Circ Res | Ma et al. 2013, Int J Cardiol | Davis et al. 2012, Circulation | Ma et al. 2011, Am J Physiol Hear Circ Physiol |