A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction.

Autor: Yokoyama R; Laboratory for Neural Information Technology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama, Toyama, 930-8555, Japan., Kinoshita K; Department of Legal Medicine, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan., Hata Y; Department of Legal Medicine, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan., Abe M; Laboratory for Neural Information Technology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama, Toyama, 930-8555, Japan., Matsuoka K; Laboratory for Neural Information Technology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama, Toyama, 930-8555, Japan., Hirono K; Department of Pediatrics, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan., Kano M; Department of Neurophysiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Nakazawa M; Department of Pediatric and Lifelong Congenital Cardiology Institute, Southern Tohoku Research Institute for Neuroscience, Southern Tohoku General Hospital, 7-115 Yatsuyamada, Koriyama, Fukushima, 963-8052, Japan., Ichida F; Department of Pediatrics, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan., Nishida N; Department of Legal Medicine, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan., Tabata T; Laboratory for Neural Information Technology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama, Toyama, 930-8555, Japan. ttabata@eng.u-toyama.ac.jp.
Jazyk: angličtina
Zdroj: Heart and vessels [Heart Vessels] 2018 Jul; Vol. 33 (7), pp. 802-819. Date of Electronic Publication: 2018 Jan 18.
DOI: 10.1007/s00380-018-1116-6
Abstrakt: We found that a female infant presenting with left bundle branch block and left ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E), SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible pathogenicity of HCN4(G811E), which results in a G811E substitution in hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole-cell HCN4 channel conductance, whereas it did not affect the gating kinetics, unitary conductance, or cAMP-dependent modulation of voltage-dependence. Immunocytochemistry and immunoblot analysis showed that the G811E mutation did not impair the membrane trafficking of the channel subunit in the heterologous expression system. These findings indicate that HCN4(G811E) may not be a monogenic factor to cause the cardiac disorders.
Databáze: MEDLINE
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