Andersen-Tawil syndrome (ATS) is a multisystem inherited disease exhibiting 
periodic paralysis, cardiac arrhythmias, and dysmorphic features. In this study, 
we characterized the KCNJ2 channels with an ATS mutation (T75M) which is 
associated with cardiac phenotypes of bi-directional ventricular tachycardia, 
syncope, and QT(c) prolongation. Confocal imaging of GFP-KCNJ2 fusion proteins 
showed that the T75M mutation impaired membrane localization of the channel 
protein, which was restored by co-expression of WT channels with T75M channels. 
Whole-cell patch-clamp experiments in CHO-K1 cells showed that the T75M mutation 
produced a loss-of-function of the channel. When both WT and the T75M were 
co-expressed, the T75M mutation showed dominant-negative effects on inward 
rectifier K+ current densities, with prominent suppression of outward currents 
at potentials between 0 mV and +80 mV over the E(K). Inside-out patch 
experiments in HEK293T cells revealed that co-expression of WT and the T75M 
channels enhanced voltage-dependent block of the channels by internal Mg2+, 
resulting in enhanced inward rectification at potentials 50 mV more positive 
than the E(K). We suggest that the T75M mutation causes dominant-negative 
suppression of the co-expressed WT KCNJ2 channels. In addition, the T75M 
mutation caused alteration of gating kinetics of the mutated KCNJ2 channels, 
i.e., increased sensitivity to intracellular Mg2+ and resultant enhancement of 
inward rectification. The data presented suggest that the mutation may influence 
clinical features, but it does not directly show this.