Models of the cardiac L‐type calcium current: A quantitative review

Abstract

The L-type calcium current (I CaL ) plays a critical role in cardiac electrophysiology, and models of I CaL are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modelling I CaL have resulted in several competing theories (encoded in mathematical equations).However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian I CaL models, and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modelling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of I CaL .

Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices

“…In our model, we focus on the voltageand Ca 2+ -gated activation and inactivation of cardiac ICa,L. We follow the idea of a multicompartmental model for the internal Ca 2+ concentrations [34] i.e., the modeled cell is divided into subvolumes, the junctional SR (JSR) and the network SR (NSR), the bulk myoplasm, and the dyadic space. When Ca 2+ enters myoplasm via cardiac L-type Ca 2+ channels or release from the SR, it results in higher local Ca 2+ concentrations near the inner membrane surface than in the bulk myoplasm.…”

“…When Ca 2+ enters myoplasm via cardiac L-type Ca 2+ channels or release from the SR, it results in higher local Ca 2+ concentrations near the inner membrane surface than in the bulk myoplasm. This, in turn, causes Ca 2+ -induced Ca 2+ release through ryanodine receptor channels (I rel ), which are present in the JSR membrane facing the dyadic clefts [27], [33], [34]. Different ionic concentrations are thus modeled for each compartment CaNSR, CaJSR, Cad, Cai, depending on the respective volumes, Ca 2+ The current through ICa,L is described by ( 3)…”

Synthesis, evaluation, and docking study of adamantyl-1,3,4-oxadiazol hybrid compounds as CaMKIIδ kinase inhibitor

“…The four distinct CaMKII isoforms (alpha, beta, gamma, and delta) are spread across different tissues: CaMKIIα, β, and γ predominantly inhabit the brain, while CaMKIIδ is primarily situated in the heart. 1,2 Within the cardiac context, CaMKIIδ is implicated in the development of heart failure, arrhythmias, and atrial fibrillation. Research has demonstrated heightened CaMKIIδ activity in individuals with heart failure and atrial fibrillation.…”

Modelling the Effect of Intracellular Calcium in the Rundown of L-Type Calcium Current

“…Models of the L-type calcium current I CaL [1] can be built by calibrating and validating them against current recorded from patch-clamp experiments. A difficulty in building I CaL models using information-rich protocols such as those used previously for hERG [2,3], lies in the interpretation of the recorded current which is attenuated with time (also called rundown).…”