11/24/2014 Medical Physiology Excitation-Contraction Coupling Eric Olson Flashcards
A motor action potential travels along a ___ to the ___ at the neuromuscular junction
motoneuron; motor endplate
The nerve endings secrete ___ which acts on a local area of the sarcolemma to open numerous acetylcholine-gated ion channels
acetylcholine
The muscle action potential propagates down ___ membranes into the interior of the muscle fiber to the ___, where it causes release of calcium ions that have been sequestered in the ___
the T-tubule (transverse tubule)
triad junction
longitudinal sarcoplasmic reticulum
The calcium ions are pumped back into the sarcoplasmic reticulum by the ___ located in the sarcoplasmic reticulum membrane, thus reducing the concentration of calcium in the sarcoplasm, and allowing the muscle fiber to relax
Ca-ATPase ion pump
Lengthening of the muscle is achieved by contraction of an ___
antagonistic muscle
What is an important difference between the events at the neuromuscular junction and the events during excitation-contraction coupling in skeletal muscle?
neuromuscular junction –> neuronal action potential
excitation-contraction coupling –> motor action potential
Acetylcholine binds the ___ receptors embedded in the ___ plasma membrane (at the motor endplate)
acetylcholine; muscle
The Acetylcholine receptors open, allowing ___ to rush into the muscle cell and depolarize the motor endplate, producing a change in the ___
sodium (Na+); endplate potential
Some ___ can also come out of the cells through the open acetylcholine receptor
potassium (K+)
The depolarized endplate potential causes nearby voltage-gated ___ in the ___ plasma membrane to open leading to the initiation of a ___ action potential that propagates down the length of the muscle fiber
sodium channels; muscle; muscle
___ quickly inactivates the released ___
acetylcholinesterase; acetylcholine
What is myasthenia gravis?
Disorder of excitation-contraction coupling caused by an autoimmune response to acetylcholine receptors
What exactly happens in MG at the cellular level?
Antibodies block or reduce the number of nicotinic acetylcholine receptors at the neuromuscular junction, resulting in muscle fatigability
Describe the diagnostic test for MG
Edrophonium test:
- edrophonium chloride (cholinesterase inhibitor) increases acetylcholine at the neuromuscular junction
- administered intravenously, it will temporarily relieve symptoms of muscle weakness, including diplopia (double vision), in myasthenia gravis
What are some other disorders of EC coupling?
Motor neuron –> ALS
Nerve –> Demyelinating disease e.g. Guillain-Barre Syndrome
Muscle –> muscular dystrophy
Sarcomere –> malignant hyperthermia
Calcium movements during contraction and relaxation in skeletal muscle (1):
The muscle action potential (AP) ___ the sarcolemma (the muscle fibers plasma membrane), including the ___.
depolarizes; transverse t-tubules;
Calcium movements during contraction and relaxation in skeletal muscle (2):
The skeletal muscle action potential is ___ dependent and ___.
sodium (Na+); brief (~2 msec)
Calcium movements during contraction and relaxation in skeletal muscle (3):
Depolarization of the T-tubules opens ___ channels (ryanodine receptors) in the sarcoplasmic reticulum (SR), releasing Ca++ i into the ___ and raising sarcoplasmic (cytosolic ) calcium [Ca++] from 10-7 M to 10-5 M.
calcium; sarcoplasm
What does it mean that the sodium dependent action potential triggered by Acetylcholine release at the neuromuscular junction triggers the release of calcium from an internal store (the SR) inside the muscle cell (muscle fiber)?
That skeletal muscle can contract in the absence of extracellular calcium
Calcium allows ___ to interact with ___, thus resulting in the development of tension
actin; myosin cross-bridges
What happens after a brief time interval, and if there are no other action potentials?
Calcium is actively transported back into the SR by a calcium ATPase ion pump, resulting in relaxation
Some calcium is bound to ___ in the SR
calsequestrin
The cycling of calcium is ___ in skeletal muscle
intracellular
Describe the T-tubule
invagination of the muscle cells plasma membrane (the sarcolemma)
Do Na+-dependent action potentials traveling on the surface of the muscle also travel down into the T-tubule?
Yes
Describe terminal cisternae
Physically attached to the T-tubule through the direct coupling of L-type calcium channels embedded in the T-tubule membrane to the Ryanodine receptors embedded in the membrane of the sarcoplasmic reticulum
Depolarization of the ___ membrane induces a change in the structure of the DHP receptor (an ___ channel) , which in turn opens a calcium channel gate in the ___ receptor in the sarcoplasmic reticulum membrane causing calcium release into the sarcoplasm (cytosoplasm) and triggering ___
t-tubule; L-type calcium; ryanodine; sarcomere contraction
What is ryanodine?
Plant alkaloid that binds to and opens SR calcium release channels (ryanodine receptors) at nanomolar concentration
Higher concentration of ryanodine (micromolar) ___ ryanodine receptors
closes
Define Calcium Induced Calcium Release (CICR)
Process by which the sarcoplasmic reticulum releases its calcium store rapidly through ryanodine receptors release
How is skeletal muscle contraction terminated?
By the removal of calcium from the sarcoplasm (cytoplasm)
What does the major mechanism for calcium removal involve?
The sarcoplasmic reticulum calcium ATPase (SERCA)
How does SERCA work?
It uses the energy of ATP hydrolysis to pump calcium back into the sarcoplasmic reticulum where it can be bound by calcium binding proteins Calreticulin and Calsequestrin
Why does skeletal muscle not require calcium influx from outside the cell (myofiber) to contract?
Because the calcium needed for contraction is released from, and then returned to the sarcoplasmic reticulum
Are there other mechanisms of calcium removal from the sarcoplasm that do extrude calcium into the extracellular fluid (outside the cell)?
Yes –>2
- plasma membrane calcium ATPase (PMCA)
- pumps 1 calcium ion out of the cell at the expense of 1 ATP molecule (using ATP hydrolysis)
- Sodium Calcium eXchanger (NCX)
- lets 3 sodium ions into the cell (down the Na+ gradient) to remove 1 calcium ion from the cell
Temporal relation between skeletal action potential, Ca and tension during a twitch:
The ___-dependent action potential (
sodium; calcium
Define summation
Increase in muscle tension from successive action potentials
Define tetanus
Maintained contraction in response to repetitive stimulation
If a tetanus oscillates, it is called ___ tetanus while a tetanus without oscillations is called ___ tetanus
unfused; fused
A single action potential produces a ___, where tension rises and then returns to baseline. However, the functional refractory period (FRP) of the AP is much ___ than the contraction time. This means that high frequency APs cause contractions that can ___. At very high frequency APs this leads to ___
twitch; shorter; summate; fused tetanus
The strength of contraction of skeletal muscle is graded by:
(1) rate coding or frequency of stimulation
(2) recruitment of additional motor units dependent
Define treppe
Steady increase in tension in successive twitches
What can produce treppe?
Repeated stimulation of the muscle at low frequency
Why is treppe NOT summation?
Because each twitch relaxes to zero tension before the next twitch initiates
In treppe successive twitches show ___ peak tension, in a step-wise fashion
greater
Treppe means stairs or steps in what language?
German
Why does treppe occur?
Because Ca++ released from previous twitches exceeds Ca++ reuptake and this results in an increase in Ca++ concentration
What does treppe result in?
An increase in the number of cross-bridges that form in the following contractions
Define motor unit
Somatic motor neuron and all the muscle fibers (myofibers) it innervates
A single ___ will innervate multiple muscle fibers BUT a single ___ is innervated by only one neuron
neuron; skeletal muscle fiber
Generally large motor units are found in ___ twitch muscle (Type II) while small motor units are found in ___ twitch (Type I) muscle
fast; slow
Are all of the innervated muscle fibers simultaneously stimulated to contract with all-or- none twitches when a motor unit is activated?
Yes
Motor units are recruited according to the ___
Size Principle
___ motor units are recruited after ___motor units as ___ force is required
Large; small; more
What happens when requirements for force are low, but control demands are high?
The ability to recruit only a few muscle fibers gives the possibility of fine control
The force generated when skeletal muscle is stimulated is related to:
- the size of the motor units stimulated
- the number of motor units activated
- the frequency of stimulation of the muscle fibers
___ is used to fuel the crossbridge cycle and to maintain ionic gradients
ATP
How does phosphocreatine act as a source of energy available to skeletal muscle?
Can rapidly transfer a high energy phosphate to ADP regenerating, but supply will last for 5-8 seconds of muscle activity
How does glycogen act as a source of energy available to skeletal muscle?
Glycogen stored in muscle is rapidly broken down to glucose, that is either metabolized anaerobically (in the absence of oxygen) to produce ATP
___ metabolism produces ATP ___, but is an inefficient process and produces ___
Anaerobic; rapidly; lactic acid
___ metabolism of glucose is ___, but is comparatively efficient and can provide sustained ATP
Aerobic; slow
Can oxidative metabolism of lipids (fatty acids) and proteins (amino acids) provide extended supplies of ATP for muscle contraction?
Yes
What produces muscle pain (burn)?
Lactic acid build up and accumulation when heavy muscle activity and low oxygen lead cause the muscle to rely on anaerobic glycolysis to produce ATP
What is the name of pain/burn caused by accumulation of lactic acid in heart muscle fiber?
Angina
What is Delayed Onset Muscle Soreness (DOMS)?
Occurs in the days following intense muscle use and associated with muscle damage, and possibly and inflammatory response
*not correlated with lactic acid levels in muscle
Define Muscle Fatigue
- decline in muscle tension as a result of previous contractile activity
- decreased shortening velocity
- slower rate of relaxation
What causes muscle fatigue?
Buildup of lactic acid and of inorganic phosphates (from phosphocreatine breakdown)
*NOT due to low ATP since a fatigued muscle still has quite high concentration of ATP
Fatigue may in fact be an adaptation to prevent ___ that will result from very low ATP level
rigor
Low ATP favors ___ actin myosin complexes, ___ calcium levels in the sarcoplasm, and therefore ___
stable; high; rigor
What causes high frequency fatigue accompanying high intensity, short duration exercise?
Failure in the conduction of action potential in the T tubule
*recovery is rapid
What causes low frequency fatigue seen with low intensity, long duration exercise?
Build up of lactic acid and phosphates which may change the conformation of muscle proteins
*recovery is slow
