Abstract
Effects of organotin compounds were studied on voltage-gated K+ current in whole-cell voltage clamped lymphocytes and in NlE-115 neuroblastoma cells. In human peripheral blood lymphocytes the immunotoxic compounds dibutyltinchloride (DBT, 2.5 μM) and triphenyltinchloride (TPhT, 2.5 μM) decrease the peak amplitude of the K+ current and prolong time to peak. Tributyltinchloride (TBT, 2.5 μM) decreases the K+ current to a greater extent than DBT and TPhT, without affecting the time to peak. The neurotoxic organotin compound trimethyltinchloride (TMT, 2.5 μM) does not affect the voltage-gated K+ current in lymphocytes. Similar effects of DBT were observed in freshly isolated and PHA-activated human lymphocytes and with rat thymocytes. On the other hand, in mouse NIE-115 neuroblastoma cells, none of the organotin compounds altered the voltage-dependent K+ current.
In human lymphocytes DBT affects both the peak amplitude and the time to peak of the K+ current in a concentration-dependent manner. At the maximum concentration of 10 μM tested, the peak amplitude of the K+ current was reduced to 22 ± 4% of the control current. The IC50 and slope factor for block of the peak outward current by DBT amounts to 6.7 ± 0.4 μM, and 2.7 ± 0.4, respectively. The delay in K+ current activation does not saturate. At 10 μM DMT increases the time to peak to 332 ± 12% of the control value. The present results suggest that the effects by DBT originate from two separate interactions with the voltage-gated K+ channel at the extracellular site of the membrane: a direct effect on the closed K+ channel causing a delay in current activation and a membrane-related effect causing inhibition of the K+ current. The differential effects of the organotin compounds may relate to their differential toxicological action.
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Oortgiesen, M., Visser, E., Vijverberg, H.P. et al. Differential effects of organotin compounds on voltage-gated potassium currents in lymphocytes and neuroblastoma cells. Naunyn-Schmiedeberg's Arch Pharmacol 353, 136–143 (1996). https://doi.org/10.1007/BF00168750
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DOI: https://doi.org/10.1007/BF00168750