VERATRIDINE ACTIONS ON 2 TYPES OF FAST NA+ CHANNELS IN HUMAN UTERINE LEIOMYOSARCOMA CELLS

In human uterine leiomyosarcoma cell line (SK-UT-1B), we previously demonstrated two types of fast Na+ current (INa(f)) induced by serum, based on different time course of current decay: fast-inactivating and slow-inactivating. To further clarify the properties of these currents, we studied the effects of veratridine, which is known to modify the inactivation process of I-Na(f), using whole-cell voltage clamp. Bath application of veratridine (100 mu M) produced a decrease in peak I-Na(f)(I-peak), simultaneous with increase in the steady-state current (I-ss) and tail current (I-tail). These effects of veratridine were observed in only slow-inactivating I-Na(f). The induction of I-ss and I-tail was completely reversed by washout of veratridine within 5 min, whereas the decreased I-peak did not recover even after 15 min of washout. These findings suggest that the fast Na+ channels in this cell line peak may have two binding sites for veratridine: a high affinity site, involved in the decrease in I-peak (possibly due to a decrease in conductance), and a low-affinity site, related to the appearance of I-ss and I-tail (due to a long opening of the channels). It is concluded that the two types of I-Na(f) in this cell line have different sensitivity to veratridine and the fast Na+ channels may have two binding sites for veratridine.