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Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain Beta-1 adrenergic receptor 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 Sodium/calcium exchanger 1 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 Dobutamine Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Dobutamine ATP H2O Ca+ ADP Pi Ca+ Ca+ Troponin Troponin G-Protein Signaling Cascade Muscle Contraction Cardiac Myocyte Sarcoplasmic Reticulum High calcium binds to troponin to displace tropomyosin from the myosin binding sites on the actin filaments Myosin and actin bind allowing the filaments to slide closer together, resulting in muscle contraction 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. High calcium activates the ryanodine receptor on the sarcoplasmic reticulum. Time Membrane potential (mV) -40mV (threshold) Pacemaker Action Potential Phase 0- depolarization Phase 3- repolarization Phase 4-spontaneous depolarization With acebutolol Without acebutolol Acebutolol, by antagonizing beta-1 adrenergic receptors, decreases intracellular Ca2+. Phase 4 spontaneous depolarization is Ca2+ dependent, therefore acebutolol decreases the slope of phase 4, increasing the time it takes for threshold to be reached and thus slows heart rate Cytosol High cytosolic calcium leads to muscle contraction Once it reaches the heart, it agonizes the beta-1 adrenergic receptor on the cell membrane of myocytes. T-tubule Dobutamine enters the bloodstream via intravenous injection
Mitochondria Calcium TPM1 TPM2 ADRB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G ATP2A2 PRKACA Dobutamine Calcium Calcium Calcium Sodium Sodium Calcium Calcium Calcium Dobutamine Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium Troponin Troponin G-Protein Signaling Cascade Muscle Contraction