Guo D, Lu Z
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA.
J Gen Physiol. 2000 Jun;115(6):799-814. doi: 10.1085/jgp.115.6.799.
Intracellular polyamines inhibit the strongly rectifying IRK1 potassium channel by a mechanism different from that of a typical ionic pore blocker such as tetraethylammonium. As in other K(+) channels, in the presence of intracellular TEA, the IRK1 channel current decreases with increasing membrane voltage and eventually approaches zero. However, in the presence of intracellular polyamines, the channel current varies with membrane voltage in a complex manner: when membrane voltage is increased, the current decreases in two phases separated by a hump. Furthermore, contrary to the expectation for a nonpermeant ionic pore blocker, a significant residual IRK1 current persists at very positive membrane voltages; the amplitude of the residual current decreases with increasing polyamine concentration. This complex blocking behavior of polyamines can be accounted for by a minimal model whereby intracellular polyamines inhibit the IRK1 channel by inducing two blocked channel states. In each of the blocked states, a polyamine is bound with characteristic affinity and probability of traversing the pore. The proposal that polyamines traverse the pore at finite rates is supported by the observation that philanthotoxin-343 (spermine with a bulky chemical group attached to one end) acts as a nonpermeant ionic blocker in the IRK1 channel.
细胞内多胺通过一种不同于典型离子孔道阻滞剂（如四乙铵）的机制抑制强整流性IRK1钾通道。与其他钾通道一样，在细胞内存在TEA的情况下，IRK1通道电流随膜电压升高而降低，最终趋近于零。然而，在细胞内存在多胺的情况下，通道电流随膜电压以复杂方式变化：当膜电压升高时，电流分两个阶段下降，中间有一个峰值。此外，与对非通透离子孔道阻滞剂的预期相反，在非常正的膜电压下仍存在显著的残余IRK1电流；残余电流的幅度随多胺浓度增加而降低。多胺这种复杂的阻断行为可以用一个最小模型来解释，即细胞内多胺通过诱导两种被阻断的通道状态来抑制IRK1通道。在每种被阻断状态下，多胺以特定亲和力和穿越孔道的概率结合。多胺以有限速率穿越孔道这一观点得到了以下观察结果的支持： philanthotoxin - 343（一端连接有庞大化学基团的精胺）在IRK1通道中起非通透离子阻滞剂的作用。
