Larsson Johan E, Frampton Damon J A, Liin Sara I
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Front Physiol. 2020 Jun 11;11:641. doi: 10.3389/fphys.2020.00641. eCollection 2020.
Voltage-gated potassium channels of the K7 family are expressed in many tissues. The physiological importance of K7 channels is evident from specific forms of disorders linked to dysfunctional K7 channels, including variants of epilepsy, cardiac arrhythmia and hearing impairment. Thus, understanding how K7 channels are regulated in the body is of great interest. This Mini Review focuses on the effects of polyunsaturated fatty acids (PUFAs) on K7 channel activity and possible underlying mechanisms of action. By summarizing reported effects of PUFAs on K7 channels and native K7-mediated currents, we conclude that the generally observed effect is a PUFA-induced increase in current amplitude. The increase in current is commonly associated with a shift in the voltage-dependence of channel opening and in some cases with increased maximum conductance. Auxiliary KCNE subunits, which associate with K7 channels in certain tissues, may influence PUFA effects, though findings are conflicting. Both direct and indirect activating PUFA effects have been described, direct effects having been most extensively studied on K7.1. The negative charge of the PUFA head-group has been identified as critical for electrostatic interaction with conserved positively charged amino acids in transmembrane segments 4 and 6. Additionally, the localization of double bonds in the PUFA tail tunes the apparent affinity of PUFAs to K7.1. Indirect effects include those mediated by PUFA metabolites. Indirect inhibitory effects involve K7 channel degradation and re-distribution from lipid rafts. Understanding how PUFAs regulate K7 channels may provide insight into physiological regulation of K7 channels and bring forth new therapeutic strategies.
K7家族的电压门控钾通道在许多组织中都有表达。K7通道的生理重要性从与功能失调的K7通道相关的特定疾病形式中可见一斑，这些疾病包括癫痫、心律失常和听力障碍的变体。因此，了解K7通道在体内是如何被调节的具有极大的研究价值。本综述聚焦于多不饱和脂肪酸（PUFAs）对K7通道活性的影响以及可能的潜在作用机制。通过总结已报道的PUFAs对K7通道和天然K7介导电流的影响，我们得出结论，普遍观察到的效应是PUFA诱导电流幅度增加。电流增加通常与通道开放的电压依赖性改变有关，在某些情况下还与最大电导增加有关。在某些组织中与K7通道相关联的辅助KCNE亚基可能会影响PUFA的作用，尽管研究结果存在矛盾。已经描述了PUFAs的直接和间接激活作用，其中对K7.1的直接作用研究最为广泛。PUFA头部基团的负电荷已被确定为与跨膜片段4和6中保守的带正电荷氨基酸进行静电相互作用的关键因素。此外，PUFA尾部双键的定位调节了PUFAs对K7.1的表观亲和力。间接作用包括由PUFA代谢产物介导的作用。间接抑制作用涉及K7通道的降解以及从脂筏中的重新分布。了解PUFAs如何调节K7通道可能有助于深入了解K7通道的生理调节机制，并带来新的治疗策略。
