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Tropomyosin alpha-1 chain Tropomyosin beta chain Beta-1 adrenergic receptor cAMP-dependent protein kinase type I-alpha regulatory subunit 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 Ryanodine receptor 2 Synaptic vesicular amine transporter Sodium- dependent noradrenaline transporter Sodium/calcium exchanger 1 Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent N-type calcium channel subunit alpha-1B Voltage- dependent T-type calcium channel subunit alpha-1H Voltage- dependent T-type calcium channel subunit alpha-1G Aromatic-L- amino-acid decarboxylase Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 cAMP-dependent protein kinase catalytic subunit alpha Norepinephrine Ca+ Norepinephrine Droxidopa Ca+ Norepinephrine Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Ca+ Ca+ Droxidopa Droxidopa Droxidopa Droxidopa ATP H2O Ca+ ADP Pi Ca+ CO2 Pyridoxal 5'-phosphate Ca+ Troponin Troponin G-protein signalling cascade Muscle Contraction Cytosol Cardiomyocyte Cytosol Postganglionic Neuron Droxidopa is converted to norepinephrine via decarboxylation. The inhibition of norepinephrine reuptake receptors by Dopamine causes more norepinephrine to accumulate in the synapse, causing the continual activation of the beta-1 adrenergic receptor When the neuron fires, the accumulation of norepinephrine from droxidopa, as well as norepinephrine already stored in the sympathetic neuron endings is released into the synapse The high concentration of norepinephrine activates the beta-1 adrenergic receptors in Cardiacmyocytes. Synapse 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 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. Synaptic Vesicle Droxidopa is administered as an oral capsule
TPM1 TPM2 ADRB1 PRKAR1A CACNA1C CACNA2D2 CACNB1 RYR2 SLC18A2 SLC6A2 SLC8A1 CACNA1A CACNA1B CACNA1H CACNA1G DDC ATP2A2 PRKACA Norepinephrine Calcium Norepinephrine Droxidopa Calcium Norepinephrine Calcium Calcium Sodium Sodium Calcium Calcium Calcium Calcium Calcium Droxidopa Droxidopa Droxidopa Droxidopa Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Carbon dioxide Calcium Troponin Troponin G-protein signalling cascade Muscle Contraction