The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

Abstract

Inward rectifier currents based on K(IR)2.x subunits are regarded as essential components for establishing a stable and negative resting membrane potential in many excitable cell types. Pharmacological inhibition, null mutation in mice and dominant positive and negative mutations in patients reveal some of the important functions of these channels in their native tissues. Here we review the complex mammalian expression pattern of K(IR)2.x subunits and relate these to the outcomes of functional inhibition of the resultant channels. Correlations between expression and function in muscle and bone tissue are observed, while we recognize a discrepancy between neuronal expression and function.

Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases

“…In addition, the s-1R KO/SOD1-G93A mouse shows enhanced neuronal activity when compared with the SOD1-G93A mouse alone (Mavlyutov et al, 2015b), suggesting that the s-1R may modulate neuronal excitability. Because activation of the s-1R leads to the inhibition of voltage-gated K 1 channels at the PM (Aydar et al, 2002;Renaudo et al, 2004;Zhang and Cuevas, 2005;Martina et al, 2007;Kinoshita et al, 2012;Kourrich et al, 2013), we speculated that this increase in excitability could be mediated via s-1R modulation of K ir 2.1, a K 1 channel that is responsible for setting the resting membrane potential in excitable cells (de Boer et al, 2010).…”

Saccharomyces cerivisiae as a model system for kidney disease: what can yeast tell us about renal function?

“…A group of unrelated ion channels has also been expressed in yeast. The Kir family is composed of seven subfamilies (Kir1-7) that share ϳ60% sequence homology and ϳ40% sequence identity within subfamilies (27). Several members of the Kir potassium channel family are expressed in the kidney, including Kir1.1, Kir4.1, Kir5.1, and Kir6.1 (27,46).…”

“…The Kir family is composed of seven subfamilies (Kir1-7) that share ϳ60% sequence homology and ϳ40% sequence identity within subfamilies (27). Several members of the Kir potassium channel family are expressed in the kidney, including Kir1.1, Kir4.1, Kir5.1, and Kir6.1 (27,46). Kir1.1 (also known as ROMK) functions at the apical membrane, and Kir4.1 and 5.1 function at the basolateral membrane of polarized epithelial cells.…”

A Little Too Much: Cardiac Electrophysiological Effects of Elevated Inward Rectifying Current Carried by the K_(IR)2.1 Ion Channel Protein

“…Currently there are 15 known K IR subunits; they have been classified in to seven subfamilies, K IR 1.x to K IR 7.x (16). Sequence homology, between subfamily is 40%, increasing to approximately 60% within subfamilies (5). In the heart numerous K IR channels have been identified, such as…”

“…Here, we will focus on K IR 2.1 channels, the highest expressed and best studied isoform in the heart. K IR 2.1 becomes also expressed in many other tissues (5) and this is likely the basis for the pleiotropic phenotype as seen in patients with KCNJ2 loss-of-function mutations.…”