Ganong's Review of Medical Physiology, 23rd Edition

(Chris Devlin) #1
CHAPTER 6
Synaptic & Junctional Transmission 119

CLINICAL BOX 6–1


Botulinum and Tetanus Toxins
Several deadly toxins which block neurotransmitter release
are zinc endopeptidases that cleave and hence inactivate pro-
teins in the fusion–exocytosis complex.
Tetanus toxin
and
botulinum toxins
B, D, F, and G act on synaptobrevin, and
botulinum toxin C acts on syntaxin. Botulinum toxins A and B
act on SNAP-25. Clinically, tetanus toxin causes spastic paraly-
sis by blocking presynaptic transmitter release in the CNS, and
botulism causes flaccid paralysis by blocking the release of

acetylcholine at the neuromuscular junction. On the positive
side, however, local injection of small doses of botulinum
toxin (botox) has proved effective in the treatment of a wide
variety of conditions characterized by muscle hyperactivity.
Examples include injection into the lower esophageal sphinc-
ter to relieve achalasia and injection into facial muscles to re-
move wrinkles.

FIGURE 6–6
Excitatory and inhibitory synaptic connections mediating the stretch reflex provide an example of typical circuits within the
CNS. A)
The stretch receptor sensory neuron of the quadriceps muscle makes an excitatory connection with the extensor motor neuron of the same muscle
and an inhibitory interneuron projecting to flexor motor neurons supplying the antagonistic hamstring muscle.
B)
Experimental setup to study excitation and
inhibition of the extensor motor neuron. Top panel shows two approaches to elicit an excitatory (depolarizing) postsynaptic potential or EPSP in the extensor
motor neuron–electrical stimulation of the whole Ia afferent nerve using extracellular electrodes and intracellular current passing through an electrode in-
serted into the cell body of a sensory neuron. Bottom panel shows that current passing through an inhibitory interneuron elicits an inhibitory (hyperpolariz-
ing) postsynaptic potential or IPSP in the flexor motor neuron.
(From Kandel ER, Schwartz JH, Jessell TM [editors]:
Principles of Neural Science,
4th ed. McGraw-Hill, 2000.)


Quadriceps
(extensor)

Hamstring
(flexor)
Inhibitory
interneuron

Spinal
cord

Extensor
motor
neuron

Current passing
Recording
Extracellular Recording
stimulating
electrodes
Ia afferent fibers
from muscle
spindles of
quadriceps

Sensory neuron
Extensor
motor neuron

Sensory
neuron
Muscle
spindle

AStretch reflex circuit for knee jerk

BExperimental setup for recording from cells in the circuit

IPSP
Motor neuron
Interneuron

Motor neuron
Sensory neuron

EPSP

Recording Current passing

EPSP

EPSP

IPSP

Ia afferent fibers
from muscle
spindles of
quadriceps

Inhibitory
interneurons
Flexor
motor
neuron

Recording

Flexor
motor
neuron
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