Updated: 1/23/2018

Action Potential Conduction

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Snapshot
  • A 36-year-old male presents with ascending muscle weakness. The patient is generally healthy, with no pertinent past medical history. He states he recently recovered from diarrhea that has lasted over a week. Neurological examination is notable for weakness in the lower extremities and an abscence of patellar reflexes. (Botulinum toxin)
Introduction
  • Action Potential Overview  
    • initiation
      • neuronal membrane potential becomes more positive → opening of voltage gated Na+ channels
        • positive feedback loop
        • threshold is reached → action potential generated
    • propagation
      • action potential generated at one portion of neuron → excitation of adjacent neuronal membrane
        • signal thus propagates down the axon via opening of voltage gated Na+ channels
    • neuromuscular junction
      • when the propagated action potential reaches the presynaptic neuron, it becomes depolarized
        • this opens voltage gated Ca2+ channels
          • allows release of acetylcholine (ACh) from stored vesicles in the presynaptic neuron
      • released ACh act on nicotinic receptors (a ligand-gated ion channel) on the motor end plate
        • motor end plate depolarizes, and propagates the action potential down the muscle fiber, ultimately leading to muscle contraction
Action Potential Initiation
  • Initiation
    • initial depolarization → opening of voltage gated Na+ channels
      • increased Na+ inflow → opening of more voltage gated Na+ channels (positive feedback loop)
        • threshold is eventually met → action potential generation
      • clinical correlate
        • tetrodotoxin (pufferfish consumption) binds fast voltage-gated Na+ channels in nerve tissue, which does not allow for depolarization or action potential formation
          • can result in nausea, weakness, dizziness or can be fatal
          • treatment is supportive
 Action Potential Propagation
  • Propagation
    • depolarized region of the neuronal membrane → excitation of adjacent neuronal membrane
    • myelinated neurons
      • Schwann cells myelinates axons of the peripheral nervous system (PNS)
        • myelinates only 1 axon
        • increases conduction velocity 
        • non-myelinated areas are called Nodes of Ranvier
          • contains a high concentration of Na+ channels
            • allows "jumping" of action potential from one Node of Ranvier to the next
              • this is saltatory conduction
        • clinical correlate
          • Guillain-Barre syndrome
            • autoimmune destruction of peripheral myelinated neurons
              • classically associated with previous Campylobacter jejuni infection
      • myelinated neuron examples
        • sensory
          • Pacinian corpuscles transmit vibrational sense and pressure via large, myelinated fibers 
    • non-myelinated neurons
      • transmit potentials via Na+ channels that exist along the entire length of the axon (no Nodes of Ranvier)
        • have same refractory period of Na+ channels as myelinated axons do but at a slower velocity of conduction due to lack of insulation (myelin)
Neuromuscular Junction

  • Neuromuscular junction 
    • propagated action potential reaches presynaptic neuron opens voltage gated Ca2+ channels
      • clinical correlate
        • Lambert-Eaton syndrome
          • autoantibodies against the presynaptic calcium channels → reduced ACh release → weakness
          • associated with small cell carcinoma of the lung
    • Ca2+ influx → ACh release with the help of SNARE proteins
      • clinical correlate
        • botulinum toxin
          • cleaves SNARE proteins → decreased ACh release → flaccid paralysis
        • tetanus toxin
          • cleaves SNARE proteins → decrease release of inhibitory neurotransmitters (GABA and glycine) in the spinal cord → spasticity and overactivity
    • released ACh act on nicotinic receptors (ligand gated ion channels) of the motor end plate
      • clinical correlate
        • myasthenia gravis
          • autoantibodies bind the post-synaptic ACh receptor → weakness
    • depolarization travels along the muscle cell via T-tubules, which are invaginations that allow for the skeletal muscle to be depolarized
    • dihydropyridine receptors are then depolarized
      • mechanically coupled to ryanodine receptors (Ca2+ release channels) on the sarcoplasmic reticulum
        • increases intracellular Ca2+ concentration → binds to troponin C → cross bridge cycle
          • See Skeletal and Cardiac Muscle Contractions topic
        • clinical correlate
          • malignant hyperthermia
            • ryanodine or dihydropyridine receptor mutation → unregulated Ca2+ release into the muscle cytoplasm → sustained muscle contraction → increased aerobic metabolism → depletion of O2, ATP, and increased CO2 production and acidosis
            • treatment: dantrolene
 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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