Aprikalim reduces the Na+-Ca2+ exchange outward current enhanced by hyperkalemia in rat ventricular myocytes Hong-Yu Li, PhD, Song Wu, PhD, Guo-Wei He,

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Aprikalim reduces the Na+-Ca2+ exchange outward current enhanced by hyperkalemia in rat ventricular myocytes Hong-Yu Li, PhD, Song Wu, PhD, Guo-Wei He, MD, PhD, Tak-Ming Wong, PhD The Annals of Thoracic Surgery Volume 73, Issue 4, Pages 1253-1259 (April 2002) DOI: 10.1016/S0003-4975(02)03381-7

Fig 1 Effects of aprikalim (APK) and Ni2+ on the Na+-Ca2+ exchange outward current activated by high potassium, in single isolated rat ventricular myocytes. (A) The experimental protocols of the study. Recording was successively made throughout the perfusion. (APK = aprikalim 100 μmol/L; HK = high potassium solution, [K+]o = 20 mmol/L.) (B) Typical current traces showing the effects of APK on the Na+-Ca2+ exchange outward current elicited by a ramp pulse during hyperkalemia ([K+]o = 20 mmol/L) and hypothermia (4°C). Recordings were made successively from one single cell. (Solid box is high [K+]o at 4°C; hatched box is high [K+]o + APK at 4°C; and open box is control at 4°C.) (C) Group results showing effects of APK (hatched bars) on the outward Na+-Ca2+ exchange current activated by high [K+]o (solid bars) at 22°C (n = 15) and 4°C (n = 6). ∗p < 0.001 versus control; #, ##p < 0.01, 0.001 versus corresponding high [K+]o; +p < 0.05 versus high [K+]o at 22°C. (D) Group result showing effects of 5 mmol/L Ni2+ (hatched bars) on the Na+-Ca2+ exchange outward current activated by high potassium (solid bars) at 22°C (n = 3) and 4°C (n = 6). ∗p < 0.001 versus control; #, ##p < 0.05, 0.01 versus corresponding high [K+]o; +p < 0.05 versus high [K+]o at 22°C. The Annals of Thoracic Surgery 2002 73, 1253-1259DOI: (10.1016/S0003-4975(02)03381-7)

Fig 2 Effects of aprikalim (APK) and Ni2+ on [Ca2+]i level during hyperkalemic/hypothermic cardioplegia in single isolated rat ventricular myocytes. (A) The experimental protocols. Recording was successively made throughout the perfusion. Patch is a solution with CsCl 2 mmol/L, BaCl2 1 mmol/L, ouabain 20 μmol/L, and verapamil 2 μmol/L, which were present in the bath solution for the patch clamp experiments. (HK = high potassium solution.) (B) Representative traces of successive recording of [Ca2+]i before, during, and after 1 hour of hyperkalemic (20 mmol/L [K+]o) and hypothermic (4°C) cardioplegia. (C) Group results showing the effects of 100 μmol/L APK and 5 mmol/L Ni2+ on [Ca2+]i during hyperkalemic/hypothermic cardioplegia. The effects of APK were also determined in the presence of 1 μmol/L glibenclamide (GBD) or in a solution with CsCl 2 mmol/L, BaCl2 1 mmol/L, ouabain 20 μmol/L, and verapamil 2 μmol/L, which were present in the bath solution for the patch clamp experiments. Values are expressed as percentage of control (mean ± SEM). (n = 25 in the Krebs 22°C group; n = 16 in the high [K+]o 4°C group; n = 9 in the high [K+]o 4°C + Ni2+ group; n = 15 in the high [K+]o 4°C + APK group; n = 6 in the high [K+]o 4°C + APK + patch solution group; and n = 8 in the high [K+]o 4°C + APK + GBD group. ∗p < 0.001 versus Krebs 22°C; #, ##, ###p < 0.05, 0.01, 0.001, respectively, versus high [K+]o at 4°C; +p < 0.05 versus high [K+]o 4°C + APK.) The Annals of Thoracic Surgery 2002 73, 1253-1259DOI: (10.1016/S0003-4975(02)03381-7)

Fig 3 The experimental protocols for the study of the contractile recovery in single ventricular myocyte. Recording was made during normal superfusion, ie, before cardioplegia, and during reperfusion, ie, after cardioplegia. For results, see Tables 1 and 2. (APK = aprikalim; HK = high potassium solution.) The Annals of Thoracic Surgery 2002 73, 1253-1259DOI: (10.1016/S0003-4975(02)03381-7)