File:WJC-8-401-g002.jpg
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Summary
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English: Milrinone causes inhibition of phosphodiesterase III enzyme which decreases cyclic adenosine monophosphate concentration by converting later into inactive 5’adenosine monophosphate. Increased cyclic adenosine monophosphate (cAMP) activates phosphokinase A (PKA) that inhibits phospholamban (PLB) by phosphorylating it. Inhibition of PLB increases uptake of calcium (Ca2+) from cytosol into the SR through sarcoplasmic reticulum calcium ATPase (SERCA). This enhanced Ca2+ entry into SR has positive impact on both systolic and diastolic function. During diastole, decreased cytosolic Ca2+ causes relaxation. During systole increased release of Ca2+ from SR store through ryanodine receptor (RyR) activation increases inotropy. However, unchecked chronic stimulation of beta-adrenoreceptor (βAR) causes inhibition of AC through Gαi protein and increases intracellular Ca2+ influx by activation of L-type calcium channel (LTCC). Activated LTCC indirectly increases intracellular Ca2+ through activation of RyR mediated release of Ca2+ from SR. This increased intracellular influx of Ca2+ is associated with increased arrhythmogenicity. ATP: Adenosine triphosphate; Gαi: G inhibitory alpha protein; Gαs: G stimulatory alpha protein; PDE: Phosphodiesterase; SNS: Sympathetic nervous system. |
Date | |
Source | https://pubmed.ncbi.nlm.nih.gov/27468333/ |
Author | Abhishek Jaiswal , Vinh Q Nguyen , Thierry H Le Jemtel , Keith C Ferdinand |
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English: This file is licensed CC BY-NC 4.0
(per https://www.wjgnet.com/bpg/gerinfo/207)
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current | 19:16, 28 November 2023 | 804 × 645 (34 KB) | Ozzie10aaaa (talk | contribs) | Uploaded a work by Abhishek Jaiswal , Vinh Q Nguyen , Thierry H Le Jemtel , Keith C Ferdinand from https://pubmed.ncbi.nlm.nih.gov/27468333/ with UploadWizard |
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