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Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain Beta-1 adrenergic receptor Adenosine receptor A1 Guanine nucleotide- binding protein G(I)/G(S)/G(T) subunit beta-1 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) Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Synaptic vesicular amine transporter Dopamine beta- hydroxylase Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Guanine nucleotide- binding protein G(i) subunit alpha-1 cAMP-dependent protein kinase catalytic subunit alpha Norepinephrine Ca+ Norepinephrine Caffeine Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Ca+ Norepinephrine Norepinephrine Caffeine Dopamine Ascorbic acid O2 Dehydroascorbic acid H2O ATP H2O Ca+ ADP Pi Ca+ Pyrroloquinoline quinone Copper 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. Cytosol High cytosolic calcium leads to muscle contraction The high concentration of norepinephrine agonizes the beta-1 adrenergic receptor on the cell membrane of myocytes. T-tubule Cytosol Presynaptic Neuron Cytosol Synaptic Vesicle Synapse Caffeine's main effects on heart rate are achieved through non-selective antagonism of adenosine A1 receptors on sympathetic neurons The antagonism of adenosine A1 receptor prevents the inhibition of norepinephrine release into the synapse. With adenosine unable to inhibit norepinephrine release, more norepinephrine accumulates in the synapse. This norepinephrine increases heart rate through the norepinephrine pathway. Increased Heart Rate
Calcium GNG2 TPM1 TPM2 ADRB1 ADORA1 GNB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G CACNA1A CACNB1 CACNA2D2 SLC18A2 DBH ATP2A2 GNAI1 PRKACA Norepinephrine Calcium Norepinephrine Caffeine Calcium Calcium Calcium Sodium Sodium Calcium Calcium Calcium Calcium Norepinephrine Norepinephrine Caffeine Dopamine Ascorbic acid Oxygen Dehydroascorbic acid Water Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium Troponin Troponin G-Protein Signaling Cascade Muscle Contraction
Ca+ GNG2 TPM1 TPM2 ADRB1 ADORA1 GNB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G CACNA1A CACNB1 CACNA2D2 SLC18A2 DBH ATP2A2 GNAI1 PRKACA Norpp Ca+ Norpp Cafeine Ca+ Ca+ Ca+ Na+ Na+ Ca+ Ca+ Ca+ Ca+ Norpp Norpp Cafeine LDP VitC O2 DHAA H2O ATP H2O Ca+ ADP Pi Ca+ Pqq Cu Ca+ Troponi Troponi PW000728 Mus Con 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. Cytosol High cytosolic calcium leads to muscle contraction The high concentration of norepinephrine agonizes the beta-1 adrenergic receptor on the cell membrane of myocytes. T-tubule Cytosol Presynaptic Neuron Cytosol Synaptic Vesicle Synapse Caffeine's main effects on heart rate are achieved through non-selective antagonism of adenosine A1 receptors on sympathetic neurons The antagonism of adenosine A1 receptor prevents the inhibition of norepinephrine release into the synapse. With adenosine unable to inhibit norepinephrine release, more norepinephrine accumulates in the synapse. This norepinephrine increases heart rate through the norepinephrine pathway. Increased Heart Rate
Ca2+ GNG2 TPM1 TPM2 ADRB1 ADORA1 GNB1 CACNA1C CACNA2D2 CACNB1 RYR2 PRKAR1A SLC8A1 CACNA1H CACNA1G CACNA1A CACNB1 CACNA2D2 SLC18A2 DBH ATP2A2 GNAI1 PRKACA Norpp Ca2+ Norpp Cafeine Ca2+ Ca2+ Ca2+ Na+ Na+ Ca2+ Ca2+ Ca2+ Ca2+ Norpp Norpp Cafeine LDP VitC O2 DHAA H2O ATP H2O Ca2+ ADP Pi Ca2+ Ca2+ Troponi Troponi PW000728 Mus Con