抄録
Ciguatoxins (CTXs) are receptor site-5 neurotoxins that open voltage-dependent Na channels, but their physiological effects are poorly understood. We studied channel modification induced by the ciguatoxin congener CTX3C (1 μmol/l) in three different Na channel isoforms (rNav1.2, rNav 1.4, and rNav1.5) transduced into HEK cells. In all three isoforms, the toxin shifted the activation potential for the Na current (V1/2 of the activation curve) in the negative direction, resulting in a 30-mV hyperpolarizing shift of threshold potential. The toxin also shortened time-to-peak current from 0.62 to 0.52 ms in rNav1.2. CTX3C shifted the inactivation potential (V1/2 of the inactivation curve) of all isoforms in the negative direction by 15 to 18 mV. CTX3C suppressed INa amplitude at -20 mV to a similar extent in all three isoforms (i.e., 80-85% of the control value). Recovery from slow inactivation induced by a prolonged (500 ms) depolarizing prepulse to 0 mV was dramatically delayed: recovery time constants were increased from 38 ± 8 to 588 ± 151 ms (n=5), 53 ± 6 to 338 ± 85 ms (n=4), and 23 ± 3 ms to 232 ± 117 ms (n = 3) in rNav1.2, rNav1.4, and rNav1.5, respectively. Thus, CTX3C exhibited a multimodal action on sodium channels, with simultaneous stimulatory and inhibitory aspects presumably related to the large molecular size and lipophilicity of this membrane-spanning toxin. [Jpn J Physiol 54 Suppl:S135 (2004)]
