FIG. 4.
Effects of ESI-05 or GGTI-298 on AP duration. (A) Whole-cell patch-clamp recording of APs obtained from an ARVM stimulated repetitively (arrows) at 1 Hz. During exposure to ESI-05, the descending phase of the AP developed a sustained plateau with oscillations in Em, characteristic of EADs. Breaks (-//-) indicate 2 and 4 min after initiation of recording. (B) Original (left) and cumulative data (right) showing AP prolongation in the presence of ESI-05 (n = 9). (C) Original (left) and cumulative data (right) showing AP prolongation in the presence of GGTI-298 (n = 13). (D) Original (left) and cumulative data (right) showing that preincubation of cells with either mitoTEMPO (30 μM, n = 6) or ranolazine (20 μM, n = 5) prevented the increase in AP duration with ESI-05. (E) Original (left) and cumulative data (right) showing that preincubation of cells with either mitoTEMPO (30 μM, n = 5) or ranolazine (20 μM, n = 5) prevented the increase in AP duration with GGTI-298. n.s.,no significant difference. ***p < 0.001. AP, action potential. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars