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Adenylate cyclase type 10 Muscarinic acetylcholine receptor M1 Myosin light chain kinase, smooth muscle PKA complex PKA complex Protein kinase C Potassium voltage-gated channel subfamily A member 1 Myosin LC-P Myosin light chain 3 Vesicular acetylcholine transporter High affinity choline transporter 1 Inositol 1,4,5- trisphosphate receptor type 1 Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent L-type calcium channel subunit alpha-1C Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent L-type calcium channel subunit alpha-1C Choline O- acetyltransferase Acetylcholinesterase Myosin light chain phosphatase Calmodulin Intermediate conductance calcium- activated potassium channel protein 4 Phospholipase C ATP-binding cassette sub-family C member 8 ATP-sensitive inward rectifier potassium channel 8 ATP-sensitive inward rectifier potassium channel 11 ATP-binding cassette sub-family C member 9 Calmodulin Voltage- dependent calcium channel subunit alpha-2/delta-1 Ca+ Acetylcholine Acetylcholine Dalfampridine K+ Acetylcholine Choline Choline Ca+ Ca+ K+ K+ Ca+ K+ K+ K+ Ca+ Dalfampridine Dalfampridine Acetyl-CoA Choline CoA H2O Acetic acid ATP cAMP Inositol 1,4,5-trisphosphate Phosphatidylinositol 4,5-bisphosphate Diacylglycerol Pi Pi Calcium Ca+ Muscle Contraction Muscle Relaxation G Protien Signalling Cascade Membrane depolarization Magnesium Calcium Magnesium Manganese Presynaptic Neuron Acetylcholine is synthesized and stored in synaptic vesicles at the nerve terminal Calcium ions stimulates the release of neurotransmitter acetylcholine into the synaptic cleft via exocytosis. Acetylcholine in the synaptic cleft activates muscarinic receptors in the neuromuscular junction, high amounts of acetylcholine causes the receptor to be more activated. Acetylcholine is broken down by acetylcholinesterase into choline and acetyl-coa Choline is taken back up into the nerve terminal and recycled to create more acetylcholine Sarcoplasmic Reticulum Cytosol Smooth Muscle Cell Unactivated PKA cannot phosphorylate calcium activated potassium channels causing potassium accumulation and promoting depolarization. Activated PKA phosphorylates the IP3 receptor to reduce its affinity for IP3. Activated PKA phosphorylates phospholipase C. There is an overall increase in calcium levels in the cytosol. Increased calcium binds readily to calmodulin. The activation of myosin light chain kinase pushes the synthesis of Myosin LC-P which leads to a high concentration of myosin LC-P and muscle contraction. Myosin binds to actin causing the filaments to slide resulting in muscle contraction. Actin Filament Myosin Filament Dalfampridine inhibits the potassium voltage-gated channel. This decreases the potassium concentration in the neuron. Since the receptor is activated, adenylyl cyclase is inhibited. Therefore, it inhibits cAMP production. Smooth Muscle The high concentration of potassium prolonges the membrane depolarization. This activates the entry of calcium by the voltage-dependent calcium transporter.
ADCY10 CHRM1 MYLK PRKAR1A PRKAR2A PRKCA KCNA1 MYL3 MYL3 SLC18A3 SLC5A7 ITPR1 CACNB1 CACNA1C CACNA2D1 CACNB1 CACNA1C CHAT ACHE PPP1CB CALM1 KCNN4 PLCB1 ABCC8 KCNJ8 KCNJ11 Unknown CALM1 CACNA2D1 Calcium Acetylcholine Acetylcholine Dalfampridine Potassium Acetylcholine Choline Choline Calcium Calcium Potassium Potassium Calcium Potassium Potassium Potassium Calcium Dalfampridine Dalfampridine Acetyl-CoA Choline Coenzyme A Water Acetic acid Adenosine triphosphate cAMP Inositol 1,4,5- trisphosphate Phosphatidylinositol 4,5- bisphosphate Diacylglycerol Phosphate Phosphate Calcium Muscle Contraction Muscle Relaxation G Protien Signalling Cascade Membrane depolarization