biostudies-literatureBriggs LENHLBI NIH HHS580-90https://www.ebi.ac.uk/biostudies/studies/S-EPMC2590500biostudies-literatureUnknown103(6)Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5 knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by reduction in ventricular expression of the cardiac voltage-gated Na+ channel pore-forming alpha-subunit (Na(v)1.5-alpha), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca2+ for contraction (conduction-contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca2+ is released from sarcoplasmic reticulum, was substantially rCirculation researchPerinatal loss of Nkx2-5 results in rapid conduction and contraction defects.PMC2590500R01 HL081577-01R01 HL081577-02HL081577R01 HL081577-03R01 HL081577-04R01 HL081577Takeda MIkeda YBriggs LELu JTCuadra AESeki TWeinberg EOHorikoshi NMarks MHOh SPKasahara HWakimoto HYasui KRaizada MKSumners CWalker AJChien KRfalsePerinatal loss of Nkx2-5 results in rapid conduction and contraction defects.Homeobox transcription factor Nkx2-5, highly expressed in heart, is a critical factor during early embryonic cardiac development. In this study, using tamoxifen-inducible Nkx2-5 knockout mice, we demonstrate the role of Nkx2-5 in conduction and contraction in neonates within 4 days after perinatal tamoxifen injection. Conduction defect was accompanied by reduction in ventricular expression of the cardiac voltage-gated Na+ channel pore-forming alpha-subunit (Na(v)1.5-alpha), the largest ion channel in the heart responsive for rapid depolarization of the action potential, which leads to increased intracellular Ca2+ for contraction (conduction-contraction coupling). In addition, expression of ryanodine receptor 2, through which Ca2+ is released from sarcoplasmic reticulum, was substantially r2008-01-01T00:00:00Z2008 Sep2026-03-16T16:43:59.663Z2019-03-26T23:49:12ZS-EPMC25905001868957310.1161/CIRCRESAHA.108.17183510.1161/circresaha.108.171835