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Tropomyosin alpha-1 chain Tropomyosin beta chain G protein complex Guanine nucleotide- binding protein G(i) subunit alpha-1 Adenylyl Cyclase Funny channel (If) Sodium/calcium exchanger 1 Inositol 1,4,5- trisphosphate receptor type 1 Voltage- dependent T-type calcium channel subunit alpha-1H Voltage- dependent T-type calcium channel subunit alpha-1G Guanine nucleotide- binding protein G(I)/G(S)/G(T) subunit beta-1 Guanine nucleotide- binding protein G(I)/G(S)/G(O) subunit gamma-12 cAMP Ca+ Ca+ Na+ Na+ Ca+ Ca+ Na+ Na+ K+ K+ Ca+ Ca+ GDP GTP ATP GTP Ca+ Muscarinic Receptor Troponin Troponin Muscle Contraction Cardiac Myocyte Sarcoplasmic Reticulum Calcium is unable to bind to troponin to displace tropomyosin from the myosin binding sites on the actin filaments Myosin and actin are not bound allowing the filaments to slide further resulting in muscle relaxation Actin Filament Myosin Filament Cytosol T-tubule GDP is replaced with GTP on the alpha subunit The G protein separates into alpha and beta/gamma subunits The G(i) alpha subunit inhibits adenylyl cyclase, lowering the production of cAMP There is an overall decrease in calcium levels in the cytosol The muscarinic receptor that activates Gi signalling causing cardiac muscle contraction is the M2 receptor, acetylcholine is an agonist of this receptor Lower cAMP concentrations means the open probability of funny channels are decreased, meaning there is less influx of ions Voltage dependent calcium channels are unable to open
TPM1 TPM2 GNG2 GNAI1 ADCY9 HCN4 SLC8A1 ITPR1 CACNA1H CACNA1G GNB1 GNG12 cAMP Calcium Calcium Sodium Sodium Calcium Calcium Sodium Sodium Potassium Potassium Calcium Calcium Guanosine diphosphate Guanosine triphosphate Adenosine triphosphate Guanosine triphosphate Calcium Muscarinic Receptor Troponin Troponin Muscle Contraction