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. 2009 Jan 7;156(2):214–225. doi: 10.1111/j.1476-5381.2008.00062.x

Figure 3.

Figure 3

(A) Selectivity of F 15845 on the main cardiac ionic currents. Persistent INa (human Nav1.5 transfected in HEK 293 cells) was induced with veratridine (4 × 10−5 mol·L−1) and elicited at −30 mV from a potential value of −80 mV. Rapid INa was elicited at −30 mV from a holding potential of −80 mV. Neuronal INa (rat Nav1.2 transfected in HEK 293 cells) was elicited at −30 mV from a potential value of −110 mV. Ito was recorded in freshly isolated rat ventricular myocytes and was elicited by a depolarizing step to +60 mV from a holding potential value of −80 mV. Inward rectifier (IK1) and delayed outward potassium currents (IKr and IKs) were recorded in freshly isolated guinea pig ventricular myocytes. IK1 was measured at −120 mV to −10 mV (20 s, 0.01 Hz) from a holding potential value of −80 mV. IKr and IKs were elicited by a depolarizing step (3 s, +60 mV) from a holding potential value of −40 mV. HERG K+ current was investigated in HEK 293 cells transfected with the KCNH2 gene and measured as outward current upon repolarization to −50 mV from a depolarization step to +60 mV. L- and T-type calcium currents were investigated in freshly isolated guinea pig ventricular myocytes. Calcium currents were elicited by incremental depolarizing steps from a holding potential value of −80 to +60 mV every 5 s. Peak T- and L-type calcium currents were measured at −30 and +10 mV respectively. (B) Effects of F 15845 on action potentials recorded in guinea pig papillary muscles. Typical action potential recordings in absence or presence of F 15845 (10−5 mol·L−1). (C) F 15845-induced changes in APD50 (left panel) and in APD90 (right panel) at a low stimulation rate (0.2 Hz) in guinea pig papillary muscles. F 15845 (10−7 mol·L−1–10−5 mol·L−1) and vehicle were tested. APD50 and APD90 values obtained at the end of 15 min superfusion were determined with respect to stabilized baseline values. Data are mean ± SEM. APD, action potential duration; F 15845, 3-(R)-[3-(2-methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5 benzoxathiepine bromhydrate; HEK, human embryonic kidney; HERG, human ether à gogo.