본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish

Pott, Alexander (Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Bock, Sarah (Molecular Cardiology, Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Berger, Ina M. (Molecular Cardiology, Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Frese, Karen (Department of Internal Medicine III, Heidelberg University Medical Center, Heidelberg, Germany ) ; Dahme, Tillman (Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Keßler, Mirjam (Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Rinné, Susanne (Institute for Physiology and Pathophysiology, AG Vegetative Physiology, Philipps-University of Marburg, Marburg, Germany ) ; Decher, Niels (Institute for Physiology and Pathophysiology, AG Vegetative Physiology, Philipps-University of Marburg, Marburg, Germany ) ; Just, Steffen (Molecular Cardiology, Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ; Rottbauer, Wolfgang (Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany ) ;
  • 초록  

    Abstract The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na + /K + -ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na + /K + -ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na + /K + -ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na + /K + -ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na + /K + -ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization. Highlights Genetic and molecular underpinnings of heart rate regulation is not fully understood yet Zebrafish has emerged as a valuable model to systematically dissect pathomechanisms of human arrhythmias N851K mutation leads to loss of Na + /K + -ATPase function in the zebrafish mutant hiphop In vitro assays demonstrate reduced hiphop Na + /K + -ATPase transmembranous pump currents Reduced Na + /K + -ATPase activity causes prolonged QT interval and myocardial refractoriness in hiphop resulting in severe bradycardia and atrioventricular block


  • 주제어

    Bradycardia .   Long-QT .   Refractoriness .   Na+/K+-ATPase .   Zebrafish .   Forward genetics.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기