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Sodium/potassium- transporting ATPase subunit gamma Tropomyosin alpha-1 chain Tropomyosin beta chain Sodium/potassium- transporting ATPase subunit alpha-1 Sodium/potassium- transporting ATPase subunit alpha-2 Sodium/potassium- transporting ATPase subunit alpha-3 Sodium/potassium- transporting ATPase subunit alpha-4 Sodium/potassium- transporting ATPase subunit beta-1 Sodium/potassium- transporting ATPase subunit beta-2 Sodium/potassium- transporting ATPase subunit beta-3 ATPase, (Na+)/K+ transporting, beta 4 polypeptide Ryanodine receptor 2 Voltage- dependent L-type calcium channel subunit alpha-1C Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent L-type calcium channel subunit beta-1 Sodium/calcium exchanger 1 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Digoxin Ca+ Na+ Na+ Ca+ Ca+ K+ K+ Ca+ Ca+ Ca+ Digoxin Ca+ Troponin Troponin Muscle Contraction Action potential Cardiac Myocyte Sarcoplasmic Reticulum 7. Calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments 9. Myosin, with an ADP and phosphate attached, binds to actin to form a cross bridge. Myosin performs a powerstroke, drawing the actin filaments together. Many actin filaments pulled together at the same time leads to muscle contraction. Actin Filament Myosin Filament Single Sarcomere Functioning Unit Time Membrane potential (mV) -40mV (threshold) Phase 0- depolarization Phase 3- repolarization Phase 4-spontaneous depolarization Without digoxin Digoxin also stimulates the parasympathetic nervous system via the vagus nerve. It slows electrical conduction in the atrioventricular node, therefore, decreases the heart rate. The rise in calcium levels leads to prolongation of phase 4 and phase 0 of the cardiac action potential Cytosol T-tubule 1. Digoxin inhibits Na+/K+ ATPase leading to high intracellular levels of Na+ 4. High concentration of calcium in the cytosol leads to calcium being transported and stored in the sarcoplasmic reticulum With digoxin AV Node Cell Action Potential 2. The sodium/calcium exchanger needs low levels of sodium in the cytosol to work. Since the concentration of sodium is high, the function of the exchanger is impaired 3. There is high levels of calcium in the cytosol since the sodium/calcium exchanger cannot function 5. An action potential arriving at the myocardium stimulates calcium channels which causes the influx of calcium into the cytosol 6. Calcium binds to and activates the ryanodine receptor, leading to the release of large amounts of stored calcium in the sarcoplasmic reticulum
FXYD2 Mitochondria TPM1 TPM2 ATP1A1 ATP1A2 ATP1A3 ATP1A4 ATP1B1 ATP1B2 ATP1B3 Unknown RYR2 CACNA1C CACNA2D2 CACNB1 SLC8A1 ATP2A2 Digoxin Calcium Sodium Sodium Calcium Calcium Potassium Potassium Calcium Calcium Calcium Digoxin Calcium Troponin Troponin Muscle Contraction Action potential