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Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain Beta-1 adrenergic receptor Inward rectifier potassium channel 2 Inward rectifier potassium channel 4 Sodium/calcium exchanger 1 Sodium channel protein type 5 subunit alpha Voltage- depenent L-type calcium channel Voltage- depenent L-type calcium channel Voltage- depenent L-type calcium channel Ryanodine receptor 2 cAMP-dependent protein kinase type I-alpha regulatory subunit Voltage-gated T-type calcium channel (ICaT) Voltage-gated T-type calcium channel (ICaT) Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 cAMP-dependent protein kinase catalytic subunit alpha Epinephrine Dronedarone Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Na+ Na+ K+ K+ Dronedarone Dronedarone ATP H2O Ca+ ADP Pi Ca+ Ca+ Troponin Troponin G-Protein Signaling Cascade Muscle Contraction Cardiac Myocyte Sarcoplasmic Reticulum Low calcium is unable to bind to troponin to displace tropomyosin from the myosin binding sites on the actin filaments Myosin and actin are unbound allowing the filaments to slide further apart, resulting in muscle relaxation Actin Filament Myosin Filament The beta-1 adrenergic receptor is coupled to and activates the G-protein signalling cascade. The G-protein signalling cascade activates protein kinase which activates calcium channels on the membrane, resulting in calcium influx. Low calcium is unable to activate the ryanodine receptor on the sarcoplasmic reticulum. Cytosol Since calcium, potassium, and sodium are linked to activation of muscle contraction. Reducing cytosolic ion levels reduces muscle contraction Epinephrine stimulation effect of the heart is reduced as intracellular ion levels are reduced by Dronedarone T-tubule Dronedarone is administered as an oral tablet Dronedarone inhibits multiple ion channels including calcium, potassium, and sodium
Calcium TPM1 TPM2 ADRB1 KCNJ2 KCNJ4 SLC8A1 SCN5A CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A CACNA1H CACNA1G ATP2A2 PRKACA Epinephrine Dronedarone Calcium Calcium Calcium Sodium Sodium Calcium Calcium Calcium Sodium Sodium Potassium Potassium Dronedarone Dronedarone Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium Troponin Troponin G-Protein Signaling Cascade Muscle Contraction