Mutation E87Q of the beta 1-subunit impairs the maturation of the cardiac voltage-dependent sodium channel

Voltage-dependent sodium channels are responsible of the rising phase of the action potential in excitable cells. These membrane integral proteins are composed by a pore-forming a-subunit, and one or more auxiliary beta subunits. Mutation E87Q of the beta 1 subunit is correlated with Brugada syndrome, a genetic disease characterised by ventricular fibrillation, right precordial ST segment elevation on ECG and sudden cardiac death. Heterologous expression of E87Q-beta 1 subunit in CHO cells determines a reduced sodium channel functional expression. The effect the E87Q mutation of the beta 1 subunit on sodium currents and a protein expression is correlated with a reduced availability of the mature form of the a subunit in the plasma membrane. This finding offers a new target for the treatment of the Brugada syndrome, based on protein maturation management. This work highlights the role played by the beta 1 subunit in the maturation and expression of the entire sodium channel complex and underlines how the defective interaction between the sodium channel constituents could lead to a disabling pathological condition.