Nerve Conduction & Neuromuscular Transmission Flashcards
Spread of electrical current down axon depends on:
- The nature of the conducting and insulating medium (cell membrane, ICF, ECF); important factors include electrical resistance of the solutions (resistance of ECF and resistance of ICF) and cell membrane, and capacitance
Spread of voltage changes occurs through the flow of electrical current carried by ions in the ICF and ECF along pathways of __ electrical resistance
Least
(more current will flow down the pathway that has less resistance)
What are the two pathways current can spread across a neuron?
- Flow across the membrane (Rm)
- Move down axon (Ri)
The ___ properties of an axon determine the conduction velocity
Cable
- determine the way graded potentials and APs propagate over space and time in an axon
What are the two important cable properties?
- time constant (τ)
- length constant (λ)
Both voltage and current ___ with time at a given magnitude
Decay
- every time there is movement 1 length constant away, there is only 30% of the initial voltage
Membrane Capacitance
ability of the cell to store charge
What factors affect the time constant?
- Rm (membrane resistance)
- Cm (membrane capacitance)
Formula for Time Constant
τ = Rm x Cm
When Rm is high, τ will ___
Increase
- current does not readily flow across the cell membrane, making it difficult to change the membrane potential
When Cm is high, τ will ___
Increase
τ is __ proportional to Rm and Cm.
Directly
Voltage decay is ___
Exponential
What happens when you have a smaller (shorter) τ?
- the more quickly a neighboring region of membrane will be brought to threshold and the sooner the region will fire an AP
- faster the speed of impulse propagation
The __ __ determines the spread of voltage changes in space
length constant (λ)
What 3 things influence λ?
- membrane resistance (Rm)
- internal resistance (Ri)
- external resistance (Ro)
Equation for Length Constant
λ = √ (Rm / Ri)
The ___ the length constant, the farther down the axon a voltage change spreads
Longer
- the longer the length constant the less the loss of signal
λ is the longest/largest when:
- Diameter of the nerve is large, meaning Ri is low (wider axon means more space for internal flow of current)
- Rm is high (increased myelination)
If the Rm could be made high or if the Ri could be made lower, the pathway down the axon would be favored and a larger portion of current would continue along the inside of the axon. In this case:
- the depolarization resulting from the AP would decay less rapidly along the axon (increased λ)
- the rate of propagation would increase (decreased τ)
Effects of Myelination on Rm and Cm:
- Myelination increases Rm, but decreases Cm
(overall effect of myelination is increased conduction velocity)
What is located in the Nodes of Ranvier?
- high concentration of voltage-gated Na channels that function in producing and sustaining a depolarization
What would happen if there were no breaks in myelination (Nodes of Ranvier)?
Neuron would be unable to generate conduction along the distance of the axon
Myelin sheath increases the distance between the conducting ICF and ECF which ____ the capacitance of the membrane
Decreases
The influx of Na+ carrying the depolarizing current during the initiation of the AP has access to the axon membrane through the:
Nodes of Ranvier
Saltatory Conduction
- the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials
- improves the speed with which a thin axon can conduct an AP along its length
What is the most common demyelinating disease of the CNS?
Multiple Sclerosis
What is the cause of MS?
- gradual demyelination of axons
Loss of myelin sheath around nerves results in:
- decrease in membrane resistance resulting in current leaking out across the membrane during conduction of local currents
- local currents decay more rapidly as they flow down the axon (decreased length constant, λ
- failure to conduct an AP occurs – demyelinated axons do not have a sufficient number of Na channels on their internodal segments and the generation of closely spaced APs is diminished
Signs and symptoms of MS:
- weakness of LE (paraparesis)
- numbness
- paresthesia (“pins and needles” sensation)
- blurred vision
- pain with eye movements
Steps of chemical synaptic transmission
(1) NT molecules synthesized and packaged into vesicles in the presynaptic nerve terminal
(2) AP arrives at the presynaptic terminal
(3) Voltage-gated Ca2+ channels on presynaptic membrane open and Ca2+ enters the neuron
(4) A rise in internal concentration of Ca2+ triggers fusion of synaptic vesicles with the presynaptic membrane
(5) NT molecules are released into the synaptic cleft and bind to specific receptors on the postsynaptic cell
(6) NT bound receptors active the postsynaptic cell
(7) NTs breakdown and are taken up by the presynaptic terminal or other cells, or diffuse away from the synapse
What two channels are found on the presynaptic membrane?
- Voltage-gated Ca2+ channels
- K+ channels (allows K+ to exit the cell)
Examples of excitatory NTs:
- ACh
- Glutamate
- Histamine
- NE
- Epinephrine
- Dopamine (BOTH)
Examples of inhibitory NTs:
- Serotonin (5-HT)
- GABA
- Glycine
- Dopamine (BOTH)
Neuromuscular Junction (NMJ)
- specialized synapse between a motor neuron and a muscle cell
- main NT: ACh
- receptors that bind ACh at the postsynaptic membrane of the muscle cell are nicotinic acetylcholine receptors (nAChRs)
Nicotinic Acetylcholine Receptors
- cation-selective, ligand-gated ion channels that mediate fast neurotransmission in the central and peripheral nervous systems
- respond the the NT ACh
Steps involved in activation of NMJ
(1) Electrical impulse propagated along axon by inflow of Na+ and outflow of K+
(2) ACh formed in nerve terminal (formation catalyzed by Choline Acetyltransferase) is packaged into vesicles
(3) AP causes voltage-gated Ca2+ channels to open and Ca2+ enters the presynaptic nerve terminal
(4) Ca2+ binds to site of active zone of presynaptic of ACh from vesicles
(5) ACh attaches to receptors of postsynaptic membrane (nAChR) at apex of junctional folds, causing channels to open for inflow of Na+ and outflow of K+, which results in depolarization and initiation of AP
(6) AP travels across sarcolemma to transverse tubules where it causes Ca2+ release from sarcoplasmic reticulum, thus initiating muscle contraction
(7) Acetylcholinesterase (AChE) degrades ACh into acetate and choline, thus terminating its activity
(8) Choline re-enters presynaptic nerve terminal to be recycled
End-Plate Potential
- stimulation of the motor nerve axon that leads to a change in its membrane potential
- def: the change in membrane potential in the muscle membrane
Excitatory Postsynaptic Potential (EPSP)
- response that occurs when the stimulation of the motor nerve cell results in depolarization in the muscle membrane
Myasthenia Gravis (MG)
- autoimmune disorder of the NMJ
- majority of patients have IgG1 and IgG3 autoantibodies – antibodies directed against the nAChRs (anti-nAChR antibodies)
- nAChR antibodies cause dysfunction at the NMJ by blocking ACh binding to nAChRs, cross-linking and internalizing nAChRs (since unable to do this will have less nAChR at postsyn memb) and activating complement-mediated nAChR destruction in the junctional folds (also means less nAChR at postsyn memb)
What molecule is an antagonist of nAChRs?
Alpha-Bungarotoxin
Clinical manifestations of MG
- characterized by weakness and fatigability of skeletal muscles
- muscle weakness may fluctuate throughout the day but it is most commonly worse later in the day or evening, or after exercise
- repetitive muscle stimulation leads to progressive lessening of the amplitude of the compound motor action potential (CMAP) as measured using electromyography
- can produce weakness in any skeletal muscle group – ocular muscles (manifesting as ptosis, eye drooping, and diplopia, double vision), mouth and throat muscles, and limb muscles
Lambert-Eaton Myasthenic Syndrome (LEMS)
- autoimmune disorder of the NMJ caused by antibodies directed against voltage-gated Ca2+ channels (VGCC)
- results in reduced ACh release from presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration and normal postsynaptic AChRs
Clinical Manifestations of LEMS
- main manifestation is slow progressive proximal muscle weakness
- autonomic dysfunction could also be present — most common manifestation of this type is a dry mouth (xerostomia)
- most patients exhibit post-exercise facilitation
Post-Exercise Facilitation of LEMS
- high frequency stimulation of a particular muscle will lead to an increase in the CMAP — this type of stimulation increases probability that Ca2+ will reach Ca2+ channel
- increase in CMAP amplitude after repetitive nerve stimulation or brief exercise in patients
- recovery of lost deep tendon reflexes or improvement in muscle strength with vigorous brief muscle activation
