as cssii is a β-toxin, it binds to site 4 on the sodium channel, thus primarily affecting the voltage sensor domain of the channel. it is thought that cssii binding to the voltage sensor domain is dependent on a conformational change of the sodium channel. the binding to site 4 induces a negative shift in voltage dependence, resulting in the aberrant opening of sodium channels. in addition, cssii reduces the peak transient current of the nav1.6 channels, and causes the occurrence of resurgent currents in cells that otherwise would not exhibit this behavior. these effects might arise from different channel binding sites for cssii, as the effects on the resurgent current occur earlier than the left shift of activation, and the transient peak current reduction. however, these additional binding sites have not yet been defined.