The Relevance of GIRK Channels in Heart Function

Abstract

Among the large number of potassium-channel families implicated in the control of neuronal excitability, G-protein-gated inwardly rectifying potassium channels (GIRK/Kir3) have been found to be a main factor in heart control. These channels are activated following the modulation of G-protein-coupled receptors and, although they have been implicated in different neurological diseases in both human and animal studies of the central nervous system, the therapeutic potential of different subtypes of these channel families in cardiac conditions has remained untapped. As they have emerged as a promising potential tool to treat a variety of conditions that disrupt neuronal homeostasis, many studies have started to focus on these channels as mediators of cardiac dynamics, thus leading to research into their implication in cardiovascular conditions. Our aim is to review the latest advances in GIRK modulation in the heart and their role in the cardiovascular system.

Redox Bridling of GIRK Channel Activity

“…Mounting evidence has implicated GIRK channel dysfunction in the pathophysiology of neurological and cardiovascular disorders. 9 , 10 However, the precise mechanisms by which GIRK channels are involved in these diseases remain incompletely understood.…”

Relevance of KCNJ5 in Pathologies of Heart Disease

“…Abnormalities in G-protein-gated inwardly rectifying potassium (GIRK) channels have been previously implicated in diseased states of the cardiovascular system; however, the complex role of GIRK4 (Kir3.4) in cardiac physiology and pathophysiology has yet to be completely understood [ 13 ]. Encoded for by the KCNJ5 gene, GIRK4 is an inwardly rectifying potassium channel subunit which can exist either with GIRK1 in a GIRK1/4 hetero-tetramer (composed of two GIRK1 and two GIRK4 subunits) or on its own as a homo-tetramer of four GIRK4 subunits (GIRK4 homo-tetramer) [ 14 ] ( Figure 1 ).…”

Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying K+ Channel 4 Mutant: In Silico Investigation in the Context of Drug Discovery for Hypertension

“…The activation of GIRK channels occurs when certain ligands, such as neurotransmitters and hormones, bind to their cognate G protein-coupled receptors [11]. This results in the dissociation of the βγ subunits of pertussis toxin-sensitive G proteins, which bind to and activate the GIRK channel [11,12]. Once the channel is opened, the outward flow of K + leads to hyperpolarization of the membrane and a reduction in cell excitability [13].…”