Biophysical Properties of a Human Disease-Causing Mutation in CaV1.3 L-Type Calcium Channels
In: Biophysical Journal, Jg. 100 (2011-02-01), Heft 3
Online
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Zugriff:
Mice lacking functional Cav1.3 L-type Ca2+-channels show sinoatrial node dysfunction and are congenitally deaf. Here we investigated the functional consequences of a homozygote mutation (insertion of an amino acid residue in a pore-forming S6-helix) in the alpha1-subunit encoding the CACNA1D gene which causes bradycardia and deafness in humans.We expressed human wildtype (WT) and mutant channel complexes (MUT) in tsA-201 cells (with alpha2delta and beta3-subunits) and recorded ON-gating (Qon) and ionic Ca2+-currents (ICa) using the whole-cell patch-clamp technique. Full length WT and MUT channel alpha1 subunit proteins were expressed at equal levels in tsA-201 membranes. In contrast to WT, MUT channels did not conduct significant ICa, but gave clear rise to Qon. WT and MUT Qon exhibited a typical nonlinear voltage-dependence of activation. Under identical experimental conditions (block of ICa by replacing Ca2+ with Mg2+ and addition of La3+ and Cd2+ in the recording solution) the half maximal activation voltage (Vh) of MUT Qon was significantly shifted by 16.2±2.8 mV (n=6-8, p
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Biophysical Properties of a Human Disease-Causing Mutation in CaV1.3 L-Type Calcium Channels
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Autor/in / Beteiligte Person: | Gebhart, Mathias ; Engel, Jutta ; Khan, Habib U. ; Mangoni, Matteo E. ; Nürnberg, Peter ; Bolz, Hanno J. ; Striessnig, Jörg ; Dafinger, Claudia ; Lieb, Andreas ; Sinnegger-Brauns, Martina J. ; Shahid Mahmood Baig ; Koschak, Alexandra |
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Zeitschrift: | Biophysical Journal, Jg. 100 (2011-02-01), Heft 3 |
Veröffentlichung: | Elsevier BV, 2011 |
Medientyp: | unknown |
ISSN: | 0006-3495 (print) |
DOI: | 10.1016/j.bpj.2010.12.3301 |
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