Novel Pathophysiological and Pharmacological insight into the Kir/KATP Channelopathies of Cardiovascular & Musculoskeletal Apparatus

The inward-rectifier potassium channels Kir1-7 family is divided into seven subfamilies according to their amino-acid homology and encoded by KCNJ genes. Despite their structural similarities, a range of mutations can occur within Kirs and accessory subunits manifesting into several channelopathies. The loss-of-function mutation in Kir2.1 causes Andersen–Tawil syndrome. This is characterized by periodic skeletal muscle paralysis, skeletal abnormalities, and biventricular tachycardia. Alternatively, the Kir2.1 gain-of-function mutation results in atrial fibrillation, a short QT syndrome and shortened cardiac action potentials.

Kir family mutations have significant effects especially in tissues highly expressing the mutant subunits. Though there is much evidence for the presence of these mutations, the consequences of these mutations to the tissue is often not investigated or neglected. This is important as this results in patients experiencing a reduced quality of life. Cantú syndrome is a recently identified channelopathy caused by the gain-of-function mutations in Kir6.1 and SUR2 subunits of KATP channels. KATP channel subunits regulate an inflammatory cell response leading to systemic damage. Though, further research is required to fully understand how these channelopathies manifest in the tissues they are expressed in.

The aim of the Research Topic is to provide pathophysiological and pharmacological insight into the role of Kir/KATP channels in their manifested channelopathies. The goal of this Topic is to accumulate research on the pathophysiological consequences of these channelopathies in affected cardiovascular and musculoskeletal apparatus and provide information on the systemic effects of the mutations. This is important to aid the identification of drug candidates to combat Kir family mutations before their effects cause significant systemic
damage. We would like to set the forum for all manuscript accepted under the scope of Frontiers in Pharmacology and welcome submissions on the following topics but not limited to:
- Consequence of mutations in channelopathies affecting cardiovascular and musculoskeletal apparatus
- The loss-of-function mutation in Kir3.4 are associated with long QT syndrome 13 in acetylcholine activated channels
- Thyrotoxic hypokalemic periodic paralysis associated with Kir2.6 loss-of-function mutations affecting skeletal muscle excitability
- Kir/KATP channels and inflammatory related manifestations in channelopathies