Fig. 9: AMPK-α1/α2 deletion reduces KV1.5 current density in pulmonary arterial myocytes. | Nature Communications

Fig. 9: AMPK-α1/α2 deletion reduces KV1.5 current density in pulmonary arterial myocytes.

From: AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death

Fig. 9

a Panels show example records for KV currents recorded during control conditions and following extracellular application of 1 µM DPO-1 in acutely isolated pulmonary arterial myocytes from (i) AMPK-α1/α2 floxed (AMPK-α1/α2 FLX) and (ii) AMPK-α1/α2 knockouts (AMPK-α1/α2 KO). b Comparison of current-voltage relationship for KV currents recorded in pulmonary arterial myocytes from AMPK-α1/α2 FLX (n = 4 cells, from n = 4 mice) and AMPK-α1/α2 KO mice (n = 5 cells from n = 4 mice) under control (normoxic) conditions and after extracellular application of 1µmol/L DPO-1. c Current-voltage relationship for DPO-1-sensitive current (current before DPO-1 minus current after DPO-1) for the experiments shown in (b). d Panels show example records for K+ currents in HEK293 cells transfected with (i) KCNA5 wild type (WT) or (ii) KCNA5 containing S559A + S592A dephospho-mimetic mutation at identified AMPK phosphorylation sites. d iii Comparison of current-voltage relationship for KV1.5 currents recorded in HEK 293 cells transfected with KCNA5 WT (n = 16 cells from n = 5 independent transfections) or S559A + S592A dephospho-mimetic KCNA5 mutant (n = 17 cells from n = 5 independent transfections paired with WT). Data are expressed as mean ± SEM. Statistical significance was assessed by two-sided paired (b) and two-sided unpaired Student’s t test (c and d iii). P values in (b) for AMPK-α1/α2 FLX vs AMPK-α1/α2 FLX + DPO-1: −20mV, * = 0.0225; −10mV, * = 0.0113; 0 mV, * = 0.0133; 10 mV, * = 0.0176; 20 mV, * = 0.0179; 30 mV, * = 0.0185; 40 mV, * = 0.0115. P values in (b) for AMPK-α1/α2 KO vs AMPK-α1/α2 KO + DPO-1: −20mV, * = 0.0291; −10mV, * = 0.0429; 0 mV, * = 0.0194; 10 mV, * = 0.0393; 20 mV, * = 0.0167; 30 mV, * = 0.0233; 40 mV, * = 0.0192. P values in (c) for AMPK-α1/α2 FLX vs AMPK-α1/α2 KO: 0 mV, * = 0.0133; 10 mV, * = 0.0117; 20 mV, * = 0.0219; 30 mV, * = 0.0850; 40 mV, ** = 0.0095. P values in diii for KCNA5 WT vs KCNA5. S559A + S592A: 10 mV; * = 0.0492; 20 mV, * = 0.0483; 30 mV, * = 0.0496; 40 mV, * = 0.045.

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