Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells
Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells
复制标题
DOI：
10.1093/toxsci/kfi097
复制
发表时间：
2005-05-01
影响因子：
3.8
通讯作者：
Bigiani, A
中科院分区：
文献类型：
--
作者：
Ghiaroni, V;Sasaki, M;Bigiani, A
雪卡毒是由海洋甲藻Gambierdiscus toxicus毒素引起的食物中毒。这种中毒的神经学特征包括感觉异常，如感觉异常、疼痛感增强以及味觉改变。在这里，我们已经评估了可能的雪卡毒素之一，甘比洛尔，味觉细胞的电压门控离子电流的影响。味细胞是具有电压门控Na+、K+和Cl-电流（分别为I-Na、I-K和I-Cl）的可兴奋细胞。通过应用膜片钳技术的单细胞在分离的味蕾从小鼠的乳头状突起，我们已经记录了这样的电流，并确定浴应用甘比尔醇的效果。我们发现，这种毒素显着抑制I-K在纳摩尔范围内（IC 50为1.8 nM），而它对I-Na或I-Cl没有显着影响，即使在高浓度（1 μ M）。即使在50分钟洗涤后，I-K的阻断也是不可逆的。除了影响电流的幅度，我们发现，甘比尔醇显着改变激活和失活过程的I-K。总之，与雪卡毒素中涉及的其他毒素（如雪卡毒素）不同，它会影响电压门控钠通道的功能，甘比尔醇的首选分子靶点是电压门控钾通道，至少在味觉细胞中是这样。电压门控钾电流在化学转导过程中放电模式的产生中起着重要作用。因此，甘比洛尔可能会改变味觉细胞的动作电位放电，这可能与临床文献中报道的味觉改变有关。
Ciguatera is a food poisoning caused by toxins of Gambierdiscus toxicus, a marine dinoflagellate. The neurological features of this intoxication include sensory abnormalities, such as paraesthesia, heightened nociperception, and also taste alterations. Here, we have evaluated the effect of gambierol, one of the possible ciguatera toxins, on the voltage-gated ion currents in taste cells. Taste cells are excitable cells endowed with voltage-gated Na+, K+, and Cl- currents (I-Na, I-K, and I-Cl, respectively). By applying the patch-clamp technique to single cells in isolated taste buds obtained from the mouse vallate papilla, we have recorded such currents and determined the effect of bath-applied gambierol. We found that this toxin markedly inhibited I-K in the nanomolar range (IC50 of 1.8 nM), whereas it showed no significant effect on I-Na or I-Cl even at high concentration (1 mu M). The block of I-K was irreversible even after a 50-min wash. In addition to affecting the current amplitude, we found that gambierol significantly altered both the activation and inactivation processes of I-K. In conclusion, unlike other toxins involved in ciguatera, such as ciguatoxins, which affect the functioning of voltage-gated sodium channels, the preferred molecular target of gambierol is the voltage-gated potassium channel, at least in taste cells. Voltage-gated potassium currents play an important role in the generation of the firing pattern during chemotransduction. Thus, gambierol may alter action potential discharge in taste cells and this could be associated with the taste alterations reported in the clinical literature.