Peripheral motor function

Purves et al., chapter 16, 1, 9
The Biology Department at SLU has a faculty member, Dr. Fisher, who does research on muscle

Review of some muscle physiology mostly not in book

Sliding filament - well covered in Bio 106 & cell - only reviewed here
Ca2+ binding to troponin gets tropomyosin off actin sites
myosin can bind actin, ATP unbinds - explaining rigor mortis in ATP depletion
Duchenne (and Becker) muscular dystrophy X linked
additional protein - dystrophin - also in brain axon terminals

Excitation - contraction coupling

Fig (not in 5th edition)
Axon and collaterals go to the huge NMJs of one motor unit

Here is a picture from our histology course of the neuromuscular junction.

Here is a transmission electron micrograph of a portion of a neuromuscular junction. Note the folds, increasing the area on the muscle cell. Note the space with electron density in the cleft. Note the numerous vesicles.

t-tubules get excitation to near sarcoplasmic reticulum
dyhydropyridine (blocking drug) receptor in t-tubule
homology to sodium channel - voltage sensitive
ryanodine receptor in sarcoplasmic reticulum same family as IP3 receptor
coupled with t-tubule

Nervous control of muscle

Fig. 16.6 p. 358

In BL A347 (General Physiology Lab) one lab goup stimulated the forearm of subject Joel with increasing frequency and obtained this record of finger twitches using a sensitive force transducer; this was our non-invasive equivalent of a tetanus experiment.

Recall that "tetanus" was the term for the disorder caused by the clostridial toxin that cleaved synaptobrevin (vSNARE).

twitches summate (to tetanus)
Types of muscle (review) - best seen in turkey
slow, actually tonic, oxidative (and hence dark meat because of hemoglobin, myoglobin and cytochrome)
fast fatigable, phasic, glycolytic
and intermediate
It is possible to stain, in this case for ATPase, to show mixed muscle cells in a muscle (dark is slow, aerobic).
autonomic nervous system (controls smooth muscle and influences cardiac muscle)

Fig. 16.5 p. 357
Motor units
In 1932, Sir Charles Sherrington won the Nobel Prize. He originated our understanding of the motor unit..

(see also Fig (section opener))
One spinal motor neuron connects to several muscle cells scattered through muscle
How many cells innervated depends on how fine vs gross the muscle's control:
13 muscle cells per nerve in extraocular muscle
1730 in calf

Fig. 16.2BC p 355
Motor unit pool - motor units to one muscle.
Spinal motor neuron cell bodies are labeled by injection of marker into the muscle (soleus vs gastrocnemius)

Also (this is a different point) each motor neuron innervates only one type (white meat, dark meat) of muscle.

Reflex

Fig. 16.10 B p 363
Stretch reflex - simplest behavior
Ia sensory -> alpha motor neuron -> muscle
alpha motor neuron to striated muscle
gamma motor neuron to intrafusal muscle (fusimotor system) to preset stretch on stretch receptor

Fig. 1.7 A,B p. 12

Fig 9.7A p 197
This pathway was also described for proprioception and in introduction
With inhibitory interneuron, there is an inhibition of the antagonistic muscle

Complex behaviors
Up to and beyond fixed action pattersn (FAPs)
built up from complex of reflexes - with many other influences
Sir Charles Sherrington Integrative action of the nervous system (1906)
1932 Nobel Prize (with Adrian) "discoveries regarding the function of neurons"

Fig. 16.14 p 367
how this integrates in spinal cord
crossed extensor reflex

Fig. 16.12 p 366
Golgi tendon organ

Fig. 16.13 p. 367
via Ib (slower than Ia) acts through inhibitory interneuron
to mediate the clasp-knife reflex -give up if stretch is too strong

More on the anatomy of the spinal cord

Fig. 16.3 p. 356
"mototopic" organization
axial (proximal) vs distal muscles - medial vs lateral
flexors vs extensors - dorsal vs ventral

Fig3. A2 p. 719
Fig. A5A p. 721 (appendix)
cervical vs. lumbar enlargements
- for all the extra motor neurons for the arms vs legs respectively

ALS

Lou Gehrig's farewell speech
http://www.youtube.com/watch?v=_SKyfGK9brs
Amyoropic Lateral Sclerosis (ALS) Box 16.D
Lou Gehrig's disease - he died in 1941 after playing baseball for the New York Yankees (retired in 1939) and (until recently) holding the record for consecutive games played
a familial variety is on chromosome 21 and codes for copper/zinc superoxide dismutase (SOD)

Recent paper

P. Aebischer & A.C. Kato, Playing defense against Lou Gehrig's Disease, Scientific American, November 2007, pp. 86-93
Cells die from cell terminal back in to cell body
Interesting that bladder and eye movement spared
Most die in a few years, Physicist Stephen Hawkins lived 4 decades

Exam questions from 2005 - 2011 relating to this outline

How do dihydropyridine and ryanodine receptors interact to enable interaction of sliding filaments?

calcium channel in t-tubule interacts with calcium channel in sarcoplasmic reticulum for calcium release

How localized, to spinal segments, would you expect to find the alpha motor neurons for a muscle like the gastrocnemius or the soleus?

might be spread over 5 segments

Say something about mototopic organization of motor neurons in the ventral horn.

proximal muscles are medial, flexors are dorsal

You withdraw one supporting leg because you stepped on something painful. What happens to the opposite leg's flexor?

it is inhibited via interneurons

Binding to troponin, helping with the release of vesicles at the "presynaptic" membrane of the neuromuscular junction, release from sarcoplasmic reticulum. Name a yet one additional location or channel for the action of calcium ions in excitation ­p; contraction coupling.
 
T-tubules carry action potentials into cell with DHP calcium channels
 
The numbers 13 vs 1730 were given for extraocular vs gastrocnemius muscles respectively (and explained in terms of muscles for fine vs gross movement respectively). 13 and 1730 what?
 
Number of muscle cells (fibers) per motor unit (one spinal motor neuron)
 
For a Golgi tendon organ in the tendon of the biceps, answer either (1) How would the muscle react from stimulation? Or (2) What is the sensory afferent axon?
 
Muscle is inhibited from contracting (via inhibitory interneuron); Ib
 
How is it that, in the knee-jerk reflex, the flexor is inhibited from contracting?
 
Through an inhibitory interneuron
 
I have located a spinal motor neuron for the triceps in the ventral horn. Where should I look, relative to that cell, for neurons that would mediate making a fist?
 
(using that diagram of making a muscle superimposed on the ventral gray matter) lateral to that neuron
 
What do dihydropyridine and ryanodine receptors have to do with each other?

dihydropyridine in t tubules interact with ryanodine in sarcoplasmic reticulum, calcium channels

Make a statement about how many different metabolic muscle types connect to one motor unit.

each motor unit has only one metabolic type

How would you go about visualizing the cell bodies of all the spinal motor neurons that connect to one muscle?

backfill from the nerve

Pick one: (1) What is the source of the signal that comes up the Ib afferent? (2) What is the function of the signal that comes up the Ib afferent?

Golgi tendon organ, let go (as opposed to contract

What is the function of the enzyme deficient in familial amyotropic lateral sclerosis?

get rid of superoxide

What cells degenerate in ALS (amyotrophic lateral sclerosis, Lou Gehrig's disease)?

spinal motor neurons

Relative to adjacent areas, what would be more plentiful in the cervical enlargement?

spinal motor neurons

In the ventral horn of the spinal cord, where are motor neurons controlling the hand relative to those controlling the shoulders?

lateral

Where is the cell body for the stretch receptor involved in the monosynaptic reflex?

dorsal root ganglion

What are gamma motor neurons used for?

to preset stretch in intrafusal muscle fibers

The sensitivity for the reflex can be preset by the fusimotor system. What type of nerve and what type of muscle are used in this efferent system?

gamma motor neuron to intrafusal system

What muscles are excited and inhibited in the crossed-extensor reflex?

ipsi + flexor to withdraw, - extensor, contra + extensor to support and - flexor

Consecutive muscle twitches that come close enough together in time fuse to a steady and stronger contraction. What is this called?

tetanus

One motor neuron connects to quite a few muscle cells. What is this called?

motor unit

There's a muscle protein called "dystrophin." Why did they give it that name?

it is the product of a gene that, if mutant, leads to Duchenne (or Becker) muscular dystrophy

Name a Ca2+ channel relevant to excitation-contraction coupling.

dihydropyridine receptor and ryanodine receptor (also synaptic calcium channel)

I compared 13 for extraocular muscle and 1730 for gastrocnemius. 13 and 1730 what?

muscle cells per neuron in a motor unit

In the knee-jerk reflex, the flexor is inhibited. How?

there is an inhibitory interneuron


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