Institute of Biophysics, National Research Council, Palermo, Italy.
PLoS One. 2012;7(5):e36867. doi: 10.1371/journal.pone.0036867. Epub 2012 May 11.
The non-specific, hyperpolarization activated, I(h) current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K(+) current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling I(h) actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on I(h) channel is able to explain virtually all experimental findings on I(h) up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by I(h).
非特异性、超极化激活的 Ih 电流特别参与癫痫，它以一种明显不一致的方式对突触整合表现出兴奋或抑制作用。有人提出，大多数不一致性可以通过与 M 型 K(+)电流的间接相互作用来调和，M 型 K(+)电流也是一种参与癫痫的电流。然而，在这里我们表明，原始实验以及用于解释和支持它们的简化模型，不能以确凿的方式解释在不同实验制剂中观察到的令人费解的 Ih 作用。相反，我们使用现实的模型表明，为什么像 TASK 样通道携带的分流电流，以及依赖 Ih 通道的电流，能够解释调制器或病理条件下 Ih 上调或下调的几乎所有实验发现。该模型的结果提出了一些可通过实验验证的预测，以更详细地描述这种难以捉摸的、特殊的相互作用，这可能对开发所有由 Ih 引起、介导或受影响的病理和认知功能障碍的新治疗方法具有重要意义。
