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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 Bupranolol Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ ATP H2O Ca+ ADP Pi Ca+ Ca+ Troponin Troponin Muscle Contraction G-Protein Signaling Cascade Cardiac Myocyte Sarcoplasmic Reticulum Calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments 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 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. 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 propranolol Without propranolol Propranolol, by antagonizing beta-1 adrenergic receptors, decreases intracellular Ca2+. Phase 4 spontaneous depolarization is Ca2+ dependent, therefore propranolol decreases the slope of phase 4, increasing the time it takes for threshold to be reached and thus slows heart rate Cytosol Since calcium is linked to activation of muscle contraction. Reducing cytosolic calcium levels reduces muscle contraction Bupranolol enters the bloodstream and once it reaches the heart, it antagonizes the beta-1 adrenergic receptor on the cell membrane of myocytes such that epinephrine stimulation of the heart is reduced. T-tubule
Mitochondria Calcium TPM1 TPM2 ADRB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G ATP2A2 PRKACA Bupranolol Calcium Calcium Calcium Sodium Sodium Calcium Calcium Calcium Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium Troponin Troponin Muscle Contraction G-Protein Signaling Cascade
Ca+ TPM1 TPM2 ADRB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G ATP2A2 PRKACA Buprano Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ ATP H2O Ca+ ADP Pi Ca+ Ca+ Troponi Troponi Mus Con PW000728 Cardiac Myocyte Sarcoplasmic Reticulum Calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments 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 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. 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 propranolol Without propranolol Propranolol, by antagonizing beta-1 adrenergic receptors, decreases intracellular Ca2+. Phase 4 spontaneous depolarization is Ca2+ dependent, therefore propranolol decreases the slope of phase 4, increasing the time it takes for threshold to be reached and thus slows heart rate Cytosol Since calcium is linked to activation of muscle contraction. Reducing cytosolic calcium levels reduces muscle contraction Bupranolol enters the bloodstream and once it reaches the heart, it antagonizes the beta-1 adrenergic receptor on the cell membrane of myocytes such that epinephrine stimulation of the heart is reduced. T-tubule
Mitochondria Ca2+ TPM1 TPM2 ADRB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G ATP2A2 PRKACA Buprano Ca2+ Ca2+ Ca2+ Na+ Na+ Ca2+ Ca2+ Ca2+ ATP H2O Ca2+ ADP Pi Ca2+ Ca2+ Troponi Troponi Mus Con PW000728