Key result
Coinjection of HERG missense mutations (T474I, A614V, V630L) with wild-type suppressed HERG current in a dominant-negative manner, with V630L and A614V shifting steady-state inactivation to negative potentials.
Population
Xenopus oocyte heterologous expression system expressing 3 novel missense mutations of HERG identified in…
Comparison
Coinjection of wild-type along with mutant cRNA vs Injection of mutant cRNA alone
Design
Preclinical
Authors
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These oocyte findings warrant no clinical change; leaves open dominant-negative HERG mechanisms in human LQT2 models.
Missense mutations of HERG cause dominant-negative suppression through multiple mechanisms, including a novel shift in voltage dependence of inactivation.
Nakajima et al. (1998) studied LQT2. HERG missense mutations (T474I, A614V, V630L) vs. Wild-type (WT) HERG was evaluated on HERG current suppression and electrophysiological properties. Coinjection of HERG missense mutations (T474I, A614V, V630L) with wild-type suppressed HERG current in a dominant-negative manner, with V630L and A614V shifting steady-state inactivation to negative potentials.
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