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Guanylate cyclase soluble subunit beta-2 Guanylate cyclase soluble subunit beta-1 Voltage- dependent L-type calcium channel subunit beta-1 Guanylate cyclase soluble subunit alpha-2 Guanylate cyclase soluble subunit alpha-3 cGMP-dependent protein kinase 1 cGMP-dependent protein kinase 2 Voltage- dependent L-type calcium channel subunit alpha-1C Voltage- dependent calcium channel subunit alpha-2/delta-2 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 Myosin light chain kinase, smooth muscle Myosin light chain 3 ABC transporter, substrate- binding lipoprotein Myosin LC-P Myosin light chain phosphatase Calmodulin-1 Glutathione S-transferase Mu 1 Calmodulin-1 Potassium voltage-gated channel subfamily D member 2 Kv channel- interacting protein 2 NO Cyclic GMP K+ K+ Ca+ Ca+ Ca+ Ca+ Isosorbide Mononitrate Isosorbide Mononitrate GTP PPi Magnesium Calcium Ca+ Muscle Relaxation Manganese Smooth muscle cell Cytosol The activation of potassium channels leads to an efflux of potassium which causes hyperpolarization of the myocyte Smooth muscle relaxation causes vasodilation of the arteries and veins Hyperpolarization The dephosphoylation of myosin light chain-phosphatase causes myosin to unbind from actin, causing muscle relaxation. The low concentration of calcium means it cannot bind to calmodulin. This prevents calmodulin from activating myosin light chain kinase which leads to an inhibitory effect and prevents muscle contraction. cGMP-dependent protein kinase also activates sarcoplasmic reticulum calcium ATPase which causes the reuptake of cytosolic calcium into the sarcoplasmic reticulum, further lowering the concentration of cytosolic calcium. Isosorbide mononitrate is metabolized into nitric oxide by the enzymes Cytochrome P450 3A Subfamily, Glutathione S-transferase Mu 1, Xanthine dehydrogenase/oxidase, or Alcohol dehydrogenase class-3 The hyperpolarization of the muscle cell inhibits voltage-gates calcium channels, which are also inhibited by protein kinase. This prevents calcium from entering the myocyte. This leads to a low concentration of cytosolic calcium. Sarcoplasmic Reticulum Myosin and actin are unbound allowing the filaments to slide further apart, resulting in muscle relaxation Actin Myosin
GUCY1B2 GUCY1B3 CACNB1 GUCY1A2 GUCY1A3 PRKG1 PRKG2 CACNA1C CACNA2D2 ATP2A1 MYLK MYL3 CDR20291_0805 MYL3 PPP1CB CALM1 GSTM1 CALM1 KCND2 KCNIP2 Nitric oxide Cyclic GMP Potassium Potassium Calcium Calcium Calcium Calcium Isosorbide Mononitrate Isosorbide Mononitrate Guanosine triphosphate Pyrophosphate Calcium Muscle Relaxation