Figure 4.

Electrophysiological Parameters of Pacemaker-like Cardiomyocytes Obtained from iSABs

(A) Distribution of pacemaker cells as shown by single-cell patch-clamp and funny-channel measurements: >81% of pacemaker-like cells were achieved; 19% of these represented immature pacemaker cells and the rest were mature pacemaker cells (n = 65). The data represent seven independent experiments and are presented as means ± SD. See also Tables S1–S3.

(B) Patch-clamp protocol. Voltage was applied to elicit the hyperpolarization-activated current for I_f recordings from isolated iSAB cells.

(C) Example of I_f current, recorded from an isolated iSAB-derived cell.

(D and E) Current density (D) and time constant of activation (E) at –130 mV, demonstrating a robust I_f expression with slow activation kinetics typical of the HCN4 channel subtype and mature SA nodal I_f (n = 17). The data represent three independent experiments and are presented as means ± SD.

(F) Reaction to β-adrenergic (isoprotenerol) and muscarinic (carbachol) stimulation leads to typical accelerated versus decelerated AP rates. iSAB-derived cells show a pronounced response to isoprotenerol, with beating rates reaching up to 560 bpm. iSAB/Iso: n = 9; iSAB/Carb: n = 5. The data represent seven independent experiments and are presented as means ± SD.

See also Figures S1 and S2.