Transient outward K+ current and a mechanosensitive current contribute to AP changes under mechanical load. (A–C) Representative APs following inhibition of Ito by 4-AP (3 mmol/L), ICl,Ca by CaCCinh-A01 (30 µmol/L), and IMSC by GsMTx-4 (5 µmol/L). (D) Load-free APD in control (Ctrl; n = 25 cells from seven animals) and following pretreatment with 4-AP (n = 10 cells from five animals), CaCCinh-A01 (CaCC; n = 6 cells from three animals), and GsMTx-4 (GsMTx; n = 6 cells from three animals). (E) Mechanical load–induced APD prolongation was more pronounced following 4-AP treatment. (F) Magnitude of mechanical load–induced APD alternans (difference between long and short APDs) was increased by 4-AP (n = 10 cells from five animals), unaltered by CaCCinh-A01 (n = 6 cells from three animals), and reduced by GsMTx-4 (n = 6 cells from three animals) compared to control (n = 19 cells from seven animals). ANOVA with Dunnett’s post hoc test.