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Human Physiology
Homework 3: Synaptic Transmission
Problem 1.
A.
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B.
Consider the stretch reflex as a model of monosynaptic reflex. Briefly describe the following:
Sensory receptor involved
The afferent neuron (also known as affector neuron)
The efferent neuron (also known as effector neuron)
The stimulus
The response
What types of electrical phenomena would you expect to be able to record along the reflex arc?
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In the axon of the sensory receptor
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In the axon of the motor neuron
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In the muscle
Problem 2
Consider a motor neuron that receives excitatory input from afferent fibers of sensory neuron and inhibitory
input coming from the motor cortex. Describe the electrical phenomena one can record from the cell body of the
motor neuron. Discuss the role of motor neuron as an integrator of afferent and efferent information.
Problem 3
A. Describe the events at the neuromuscular junction following arrival of AP. Specifically discuss:
 Presynaptic (in the axon terminal) changes in intracellular concentration of Na+, K+, Ca2+
 Presynaptic events following increase of intracellular calcium concentration
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Events in the synaptic cleft
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Postsynaptic (in the muscle) changes in intracellular concentration of Na+, K+, Ca2+
B. Describe what will happen to the sequence of events discussed in A. following application of:
 Na+ channel blocker
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Ca2+ channel blocker
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Botulinum toxin
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Human Physiology
Homework 3: Synaptic Transmission
Case Study – Group seeks Botox warning after 16 death reports
By Lisa Richwine Thu Jan 24 2008, 8:16 PM ET
WASHINGTON (Reuters) - Botox and a similar injection should come with stronger warnings following
reports of 16 deaths after the botulinum toxin spread inside the body, a U.S. consumer group said on Thursday.
Public Citizen asked U.S. authorities to require the strongest possible warning, highlighted in a "black box," on
Allergan Inc's Botox and Solstice Neurosciences Inc's Myobloc.
Botox is famous for smoothing facial wrinkles but also has approved medical uses such as treating cervical
dystonia, or rigid neck muscles. Myobloc is cleared only for the neck condition.
Both injections are made with forms of the botulinum toxin, which blocks nerve impulses to muscles and makes
them relax.
Public Citizen said it reviewed 180 reports submitted to the Food and Drug Administration by manufacturers
involving patients injected with Botox or Myobloc. The reports detailed cases of muscle weakness, difficulty
swallowing or aspiration pneumonia, a serious condition caused by breathing a foreign material into the lungs.
Reports to the FDA do not prove a product caused a particular problem, but the agency uses them to look for
patterns of potential complications. Experts believe most problems are under-reported to the agency.
"There are no safety issues raised in the petition that are not already addressed in the labeling for Botox,"
Allergan said in a statement. The company said it is in frequent dialogue with the FDA to ensure proper labeling
and also submits all information it receives on adverse events whether or not they are related to the drug.
Solstice Neurosciences said in a statement that it recently submitted safety data to the FDA and it stood behind
the current prescribing information.
Allergan projected in November that worldwide sales for Botox would top $1.1 billion in 2007.
Sixteen cases reported to the FDA were fatal, including four involving children under 18, Public Citizen said.
Eighty-seven patients were hospitalized.
Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said such problems can occur if
botulinum toxin spreads from the injection site to places such as the esophagus, causing partial paralysis.
Instructions for Botox and Myobloc mention the issue but it is easy to miss, he said.
Public Citizen asked the FDA to order a black-box warning to highlight the concern, plus a letter to doctors. The
agency also should require a consumer-friendly guide explaining the risks that would be handed out by doctors
when the drug is injected, the group said.
"These significantly improved warnings to doctors and patients would increase the likelihood of earlier medical
intervention when symptoms of adverse reactions to botulinum toxin first appear, and could prevent more
serious complications, including death," Public Citizen said in a petition to the FDA.
Early symptoms include dry mouth, difficulty breathing or swallowing, slurred speech, drooping eyelids and
muscle weakness.
The group said European regulators have warned physicians to watch for signs of botulinum toxin
complications.
FDA spokeswoman Karen Riley said the agency would not comment while the Public Citizen petition was
under review.
Questions:
What botulinum toxin does to neurons?
Why Botox is popular in the first place (need cellular lever explanation)?
What is the mechanism of “muscle weakness” in some patients injected with Botox?
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