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Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain Beta-1 adrenergic receptor cAMP-dependent protein kinase type I-alpha regulatory subunit Voltage- depenent L-type calcium channel Ryanodine receptor 2 Sodium/calcium exchanger 1 Voltage-gated T-type calcium channel (ICaT) Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 cAMP-dependent protein kinase catalytic subunit alpha Isoproterenol Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Isoproterenol ATP H2O Ca+ ADP Pi Ca+ Ca+ Troponin Troponin G-protein signalling cascade Muscle Contraction Cardiac Myocyte Sarcoplasmic Reticulum Calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments Myosin binds to actin bringing the filaments together and causing muscle contraction Actin Filament Myosin Filament Isoprpterenol binds to and activates the beta-1 adrenergic receptor. 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 Without isoprenaline With isoprenaline Isoprenaline increases intracellular Ca2+. Phase 4 spontaneous depolarization is Ca2+ dependent, therefore isoprenaline increases the slope of phase 4, allowing threshold to be reached faster and increasing heart rate Cytosol Isoprenaline is administered via intravenous injection
Mitochondria Calcium TPM1 TPM2 ADRB1 PRKAR1A CACNA2D2 RYR2 SLC8A1 CACNA1G ATP2A2 PRKACA Isoproterenol Calcium Calcium Calcium Sodium Sodium Calcium Calcium Calcium Isoproterenol Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium Troponin Troponin G-protein signalling cascade Muscle Contraction