Department of Surgery, Division of Cardiac Surgery, The Ohio State University, Columbus, OH 43210, USA.
The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
Int J Mol Sci. 2023 Jun 29;24(13):10849. doi: 10.3390/ijms241310849.
Abnormalities in G-protein-gated inwardly rectifying potassium (GIRK) channels have been implicated in diseased states of the cardiovascular system; however, the role of GIRK4 (Kir3.4) in cardiac physiology and pathophysiology has yet to be completely understood. Within the heart, the K channel, consisting of two GIRK1 and two GIRK4 subunits, plays a major role in modulating the parasympathetic nervous system's influence on cardiac physiology. Being that GIRK4 is necessary for the functional K channel, , which encodes GIRK4, it presents as a therapeutic target for cardiovascular pathology. Human variants in have been identified in familial hyperaldosteronism type III, long QT syndrome, atrial fibrillation, and sinus node dysfunction. Here, we explore the relevance of in each of these diseases. Further, we address the limitations and complexities of discerning the role of in cardiovascular pathophysiology, as identical human variants of have been identified in several diseases with overlapping pathophysiology.
G 蛋白门控内向整流钾 (GIRK) 通道的异常与心血管系统疾病状态有关；然而，GIRK4（Kir3.4）在心脏生理学和病理生理学中的作用尚未完全被理解。在心脏中，由两个 GIRK1 和两个 GIRK4 亚基组成的 K 通道在调节副交感神经系统对心脏生理学的影响方面起着主要作用。由于 GIRK4 是功能性 K 通道的必要条件，该基因编码 GIRK4，因此它成为心血管病理学的治疗靶点。已经在家族性醛固酮增多症 III 型、长 QT 综合征、心房颤动和窦房结功能障碍中鉴定出人类中的 。在这里，我们探讨了 在这些疾病中的相关性。此外，我们还解决了在心血管病理生理学中辨别 的作用的局限性和复杂性，因为在几种具有重叠病理生理学的疾病中已经鉴定出 相同的人类变体。
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