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What is Digoxin increases cardiac contractility by directly engaging in wof and explain in detail?
Mechanism of action:- Digoxin increases force of cardiac contraction by a direct action independent of innervation. It selectively binds to extracellular face of the membrane associated Na+K+ ATPase of myocardial fibres and inhibitis this enzyme. Inhibition of this cation pump results in progressive accumulation of Na+ intracellularly. This indirectly results in intracellular Ca2+ accumulation. During depolarization Ca2+ ions enter the cell driven by the steep Ca2+ gradient through voltage sensitive L type Ca2+ channels. This triggers release of larger amount of Ca2+ stored in sarcoplasmic reticulum (SR) through Ryanodine calcium channel 2 (RYR2) - cytosolic Ca2+ increases transiently (calcium transients) - triggers contraction by activating troponin C on myofibrils. Ref:- kd tripathi; pg num:-514