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.

From: Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

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