Cardiac muscle physiology

Figures

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  Fig 1. Regional differences in cardiac action potential configurations. Schematic cross section of the heart depicting the corresponding action potential configuration from different regions of the heart indicated by arrows. Colour-coded sections on the action potentials refer to the corresponding sections on the schematic electrocardiogram (ECG). Note the characteristic action potential of contractile cells with a flat baseline and a plateau phase. Regional differences in action potential duration exist within the myocardium to ensure one-way conduction of depolarisation preventing re-entrant circuits. Pacemaker cells do not have a stable resting membrane potential but are characterised by their slow spontaneous diastolic depolarisation and they also have no plateau phase. AVN, atrioventricular node; Endo, endocardial; Epi, epicardial; Mid, midmyocardial; SAN, sinoatrial node. Reproduced from Varro 2020 et al.,5 licensed under Creative Commons Attribution CC-BY 4.0.

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  Fig 2. Tissue-specific (human) cardiac atrial, Purkinje fibre, and ventricular action potentials and the underlying ionic currents in different action potential phases, indicating their pharmacology and modulation. Black arrows indicate inward and yellow arrows indicate outward current. The contributions of different currents to the action potentials are indicated below the action potentials, with a time course adjusted to the action potential. CaM, calmodulin; CaMKII, Ca2+-calmodulin kinase II; hERG, human ether-à-go-go-related gene; IK1, inward rectifier potassium current; IK,Ach, acetylcholine-activated potassium current; INa, sodium current; ICaL, L-type calcium current; ICaT, T-type calcium current; If, funny/pacemaker current; Ito, transient outward current; IKCa, calcium-activated potassium current; IKr, IKs, and IKur, rapid, slow, and ultrarapid components of delayed rectifier potassium current; Kir, inward rectifier potassium channel; KV, voltage-gated potassium channel; NaV, voltage-gated sodium channel; TASK, tandem of pore domains in a weak inward rectifying potassium channel (TWIK)-related acid-sensitive potassium channel; TTX, tetrodotoxin. Reproduced from Varro 2020 et…

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  Fig 3. Diagram of a section of the sarcomere to show the arrangement of the thick and thin myofilaments. Cytoskeletal proteins form the Z- and M-lines that run transversely across the cardiomyocyte, with the thin and thick myofilaments interdigitating between adjacent Z-lines. Also illustrated are two giant proteins, titin and nebulin, that support the thick and thin filaments respectively. Adapted with permission from Hopkins.6.

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  Fig 4. A simplified pictorial representation of the actin-myosin structure with (RLCs). The diagram shows the thick (myosin containing, red) filament backbone and thin (actin containing, white circles represent actin monomers) filament with an actin-myosin cross-bridge. The essential myosin light chain (ELC, yellow box) and phosphorylated regulatory myosin light chains (RLC, blue box) are in the neck region of the myosin heavy-chain monomer. The myosin head interacts weakly or strongly with the thin filament forming a cross-bridge structure. The troponin complex (purple oval) on the thin filament comprised of troponin C, troponin I, and troponin T activate muscle contraction via calcium binding. Myosin binding protein C (MyBP-C) (cyan) is associated with the thick filament backbone and also interacts with the thin filament (not drawn to scale). Reproduced from Yu et al., 2016,19 licensed under Creative Commons Attribution CC-BY 4.0.

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  Fig 5. The effect of regulatory myosin light chain (RLC) phosphorylation on myosin head and lever arm arrangement. With RLC in the unphosphorylated state, the myosin globular head and lever arm regions are in conformational equilibrium between lying/binding to the thick filament backbone surface (OFF state) and moving away towards the thin filament (ON state). This equilibrium is shifted towards the ON state upon RLC phosphorylation, possibly a result of weakened electrostatic interaction between the added phosphate and negatively charged thick filament surface. The entire thick filament arrangement of myosin heads and other sarcomeric proteins (MyBP-C, troponin complex etc.) are not shown for simplicity. ELC, essential myosin light chain. Not drawn to scale. (Note: The ON and OFF states mentioned here are not related to the activation/deactivation with calcium binding/unbinding to Troponin C.) Reproduced from Yu et al., 2016,19 licensed under Creative Commons Attribution CC-BY 4.0.