Small and Intermediate Calcium Activated Potassium Channels in the Heart: Role and Strategies in the Treatment of Cardiovascular Diseases.

David Weisbrod

doi:10.3389/fphys.2020.590534

Abstract

Calcium-activated potassium channels are a heterogeneous family of channels that, despite their different biophysical characteristics, structures, and pharmacological signatures, play a role of transducer between the ubiquitous intracellular calcium signaling and the electric variations of the membrane. Although this family of channels was extensively described in various excitable and non-excitable tissues, an increasing amount of evidences shows their functional role in the heart. This review aims to focus on the physiological role and the contribution of the small and intermediate calcium-activated potassium channels in cardiac pathologies.

Highlights

Specialty section: This article was submitted to Cardiac Electrophysiology, a section of the journal Frontiers in Physiology
Grissmer and his colleagues already raised the hypothesis of the interaction of a single calmodulin per monomer, based on the estimated Hill coefficient of the apamin-sensitive conductance that they isolated from human T-lymphocytes (Grissmer et al, 1992)
Despite the major advances in cardiovascular pharmacology, disease registries show that the management of cardiac arrhythmia and heart failure (HF) did not benefit from this mortality reduction (Cheng et al, 2018)

Summary

David Weisbrod*

Edited by: Pietro Mesirca, INSERM U1191 Institut de Génomique Fonctionnelle (IGF), France. SK calcium-activated potassium channels are constitutively binding calmodulin protein (CaM), which plays the role of a Ca2+ sensing β-subunit Grissmer and his colleagues already raised the hypothesis of the interaction of a single calmodulin per monomer, based on the estimated Hill coefficient of the apamin-sensitive conductance that they isolated from human T-lymphocytes (Grissmer et al, 1992). In a transient expression system, rSK2 phosphorylation by PKA is associated with a reduction of the channel expression at the cell membrane (Ren et al, 2006) This regulation seems C-terminal specific, since SK trafficking is not altered when the three “major” Serine residues are replaced by non-phosphorable amino acids. The open probability of SK channels is increased after phosphorylation by calmodulin kinase II (Kong et al, 2000)

Expression and Role in the Heart

Implication in Cardiopathologies

Implication in Cardiac Disorders and Arrhythmia

Findings

DISCUSSION