Antiarrhythmic Effects of Dantrolene in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia and Replication of the Responses Using iPSC Models
Fig 5
Characterization of CPVT-iPSCs derived CMs.
(A) Immunocytochemical stainings of cardiac markers where red represents troponin T, green connexin-43 and blue DAPI-staining for nuclei. Scale bars 200 μm. (B) Representative traces of a control CM showing normal regular Ca2+ transients and CPVT1 CMs showing abnormalities like multiple peaks, low peaks, irregular phases and oscillations in Ca2+ handling. (C) Quantification of percentage of CPVT1 and control iPSC CMs exhibiting abnormal Ca2+ transients at baseline (bl) and during adrenaline perfusion (adr). (D) Frequency and (E) Diastolic level of intracellular Ca2+ of all CPVT1 and control CMs. Numbers of cells analyzed in C, D, and E, exon 3 del n = 48, P2328S n = 72, T2538R n = 52, L4115F n = 110, Q4201R n = 63, V4653F n = 29, Controls (WT) n = 28. As an exception, number of WT cells analyzed in D, and E, in bl n = 54 and adr n = 27 and number of P2328S cells in bl n = 90 and adr n = 47. Grey bars indicate cells at baseline and black bars during adrenaline perfusion. Error bars, SEM. *P<0.05 CPVT1 versus control, with Student’s t-test. Significance’s of mutation specific differences, see S2 Table.