Absence of a trafficking defect in R1232W/T1620M, a double SCN5A mutant responsible for Brugada syndrome.
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.


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.
Makita
Naomasa
N
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
Mochizuki
Naoki
N
Tsutsui
Hiroyuki
H
D053840:Brugada Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D010957:Plasmids; D021381:Protein Transport / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D012964:Sodium