Naomasa Makita1, Naoki Mochizuki, Hiroyuki Tsutsui. 1. Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. makitan@med.hokudai.ac.jp
Abstract
BACKGROUND: A trafficking defect of mutant cardiac Na-channels (SCN5A) has been implicated in Brugada syndrome. Although R1232W polymorphism and T1620M mutation by themselves have little effect on Na-channel function, their combination has been reported to disrupt membrane trafficking, resulting in a non-functioning Na channel. METHODS AND RESULTS: Contrary to previous findings, patch-clamp recordings of heterologously expressed R1232W/T1620M showed robust Na currents and confocal microscopy exhibited predominant expression in the plasma membrane, similar to the wild-type channel. CONCLUSIONS: It is unlikely that an intragenic interaction between R1232W and T1620M of SCN5A causes a trafficking defect leading to a non-functioning Na channel.
BACKGROUND: A trafficking defect of mutant cardiac Na-channels (SCN5A) has been implicated in Brugada syndrome. Although R1232W polymorphism and T1620M mutation by themselves have little effect on Na-channel function, their combination has been reported to disrupt membrane trafficking, resulting in a non-functioning Na channel. METHODS AND RESULTS: Contrary to previous findings, patch-clamp recordings of heterologously expressed R1232W/T1620M showed robust Na currents and confocal microscopy exhibited predominant expression in the plasma membrane, similar to the wild-type channel. CONCLUSIONS: It is unlikely that an intragenic interaction between R1232W and T1620M of SCN5A causes a trafficking defect leading to a non-functioning Na channel.
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