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001-es BibID:	BIBFORM114618
035-os BibID:	(cikkazonosító)14659 (scopus)85169763616 (WoS)001062861100018
Első szerző:	Magyar Zsuzsanna Édua (molekuláris biológus)
Cím:	Function of a mutant ryanodine receptor (T4709M) linked to congenital myopathy / Magyar Zsuzsanna É., Hevesi Judit, Groom Linda, Dirksen Robert T., Almássy János
Dátum:	2023
ISSN:	2045-2322
Megjegyzések:	Physiological muscle contraction requires an intact ligand gating mechanism of the ryanodine receptor 1 (RyR1), the Ca2+-release channel of the sarcoplasmic reticulum. Some mutations impair the gating and thus cause muscle disease. The RyR1 mutation T4706M is linked to a myopathy characterized by muscle weakness. Although, low expression of the T4706M RyR1 protein can explain in part the symptoms, little is known about the function RyR1 channels with this mutation. In order to learn whether this mutation alters channel function in a manner that can account for the observed symptoms, we examined RyR1 channels isolated from mice homozygous for the T4709M (TM) mutation at the single channel level. Ligands, including Ca2+, ATP, Mg2+ and the RyR inhibitor dantrolene were tested. The full conductance of the TM channel was the same as that of wild type (wt) channels and a population of partial open (subconductive) states were not observed. However, two unique sub-populations of TM RyRs were identified. One half of the TM channels exhibited high open probability at low (100 nM) and high (50 ?M) cytoplasmic [Ca2+], resulting in Ca2+-insensitive, constitutively high Po channels. The rest of the TM channels exhibited significantly lower activity within the physiologically relevant range of cytoplasmic [Ca2+], compared to wt. TM channels retained normal Mg2+ block, modulation by ATP, and inhibition by dantrolene. Together, these results suggest that the TM mutation results in a combination of primary and secondary RyR1 dysfunctions that contribute to disease pathogenesis.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Biophysics Mechanisms of disease Pathogenesis Permeation and transport Physiology
Megjelenés:	Scientific Reports. - 13 : 1 (2023), p. 14659. -
További szerzők:	Hevesi Judit (1990-) (fogorvos) Groom, Linda Dirksen, Robert T. Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító)
Pályázati támogatás:	NKFIH FK144576 Egyéb ÚNKP-22-4-I-DE-28 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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