Stimulated Excitable Cells Flashcards
What are the types of excitable cells?
Excitable Cells = cells that can fire APs
– Neurons
• APs are critical for neuronal communication
• Neurons integrate inputs and fire AP to trigger release of neurotransmitter
– Muscle
• Skeletal: contraction driven by Na+-mediated AP
• Cardiac: myocyte contraction, sinoatrial (SA) node generates APs to set pacemaker rhythm
• Smooth: Ca2+ mediates depolarisation and contraction
– Some endocrine cells
• e.g., pancreatic β cells, pituitary
What are the stimulus-response characteristics?
• Receptive endings of neurons respond electrically to specific stimuli
– Primaryafferents:touch,sound, light, heat, etc.
• Local reactive electrical potentials are graded
– Vm change varies with the magnitude of the stimulus
• Receptor potentials (graded)
– in sensory receptive zone
Describe signal transduction
• Receptors for specific stimuli are linked to ion channels
– Direct link: receptor and channel are part of the same molecule, e.g. ACh receptor at neuro-muscular junction (fast)
– Indirect link: via 2nd messenger systems (slower)
– Stimulation causes change in ion conductance and Vm
• Post-synaptic potentials (graded)
– In post-synaptic dendrites receiving chemical inputs from pre-synaptic neurons
What is the length constant?
Receptor potentials and postsynaptic potentials are decremental, i.e., they get smaller with more distance from the site of initiation
• Length constant λ (lambda)
– Distance over which a graded potential decays to 37% (1/e) of its maximal amplitude
– Greater λ means less decrement over distance
– Depends on intracellular (ri) and transmembrane resistance (rm)
– Typical λ values for neurons are 0.1-1.5 mm, i.e., depolarization spreads locally only over short distances
What are the length constant and cable properties?
Compared to small axons, larger diameter axons have
– Internal cross-sectional area
• larger
– Intra-axonal resistance to ion flux
• Less
– Lengthconstant
• Greater
– Conductionspeed
• Greater
Examples (diameter and conduction velocity shown)
– Human small unmyelinated fibre: 0.2 – 1.5 μm, 0.5 - 2 m/s
– Squid giant axon: 0.5 – 1 mm, 20 - 25 m/s
How does axonal diameter affect conduction velocity?
Small-diameter axon -> small cross-sectional area -> high intracellular resistance -> short length constant
Large diameter axon -> large cross-sectional area -> low intracellular resistance -> long length constant
How does axonal diameter affect conduction velocity?
Small-diameter axon -> small cross-sectional area -> high intracellular resistance -> short length constant
Large diameter axon -> large cross-sectional area -> low intracellular resistance -> long length constant
How does AP initiation occur?
Input integration
– Graded potentials generate an AP if their sum exceeds the depolarization threshold at a special axonal region
• Impulse Initiation Zone (IIZ)
– Near axonal hillock (at start of axon), or near sensory nerve endings in sensory neurons
– Contains the highest density of voltage-gated Na+ channels
– Most excitable part of neuron
– Site of AP initiation
What is the Nav structure-function relationship?
• 4 α subunits, each has 6 transmembrane domains
• S4 is positively charged, confers voltage sensitivity
• S5 and S6 line the inner ion pore
• Rings of amino acids around pore confer ion selectivity
• Intracellular loops: inactivation gate (D3-D4 short link)
and phosphorylation sites (long intracellular links)
What is the Nav activation gate?
The S4 transmembrane domain confers voltage sensitivity: Positively charged amino acids move outwards on depolarization, because the inside becomes more positive, pushing positive charges out. This opens the central pore and constitutes the activation (m) gate.
What is the Nav inactivation gate?
Outward movement of the S4 transmembrane domain with depolarization also exposes amino acids on the internal S4-S5 links that bind the IFMT (isoleucine, phenylalanine, methionine and threonine) motif in the short D3- D4 intracellular link. The bound inactivation (h) gate blocks ion flux
What is Saltatory conduction ?
• Myelin sheaths
– Wrap short axon segments
– FormedbySchwanncellsin PNS, oligodendrocytes in CNS
– Rich in lipids, act as electrical insulator
• AP ‘jumps’ from one unmyelinated node of Ranvier to the next, between the myelinated sections
• More energy-efficient and
much faster AP conduction
Describe rapid conduction in myelinated axons
• Unmyelinated axon (top)
• Current from depolarized region
depolarizes adjacent region, conducting the AP
• Myelinated axon (bottom)
• Current from a depolarized
node of Ranvier cannot depolarize directly adjacent regions since they are insulated (myelinated)
• But the current is sufficient to depolarize the next, making the AP ‘jump’ from node to node
• Since the insulated sections don’t need to be depolarized (which takes time), AP conduction is much faster.
How did measured size and conduction velocity diminished?
Measured human nerve conduction velocity (NCV) in major peripheral nerves of the arms and legs would normally be in the range 40-65 m/s. Significant slowing or even failure AP transmission indicates deficits in AP conduction, possibly due to an electrolyte disturbance, ion channel abnormality or demyelinating disease. More in the PNS disorders lecture
What are the disorders of myelination?
• Diseases that lead to myelin sheath damage, slow or blocking AP conduction
• Some examples (more detail in PNS disorders lecture) :
– CNS
• Myelinoclastic disorders (myelin is being destroyed) – Usually autoimmune, e.g. multiple sclerosis (MS)
• Leukodystrophic disorders (myelin is not properly produced) – e.g., CNS neuropathies due to vitamin B12 deficiency
– PNS
• Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy, both autoimmune conditions targeting Schwann cells
- Symptoms include muscle weakness, loss of muscle control, ataxia, loss of sensation, paresthesias (abnormal sensations)
- Diagnostic methods include tendon reflex testing (e.g. patellar or Achilles tendon), MRI (to detect larger lesions), and electrodiagnostics such as nerve conduction velocity studies
