Ch. 9 Muscular Sys. II Physiology of skeletal Muscle Fibers Flashcards
I. The Nerve Stimulus and Action Potential
- The nerve cells that activate skeletal muscle fibers are called somatic motor neurons, or neurons of the somatic (voluntary) nervous system .
- Their cell bodies “reside in the brain or spinal cord, and their long threadlike extensions called axons, bundled within nerves, transmit electrical signals (impulses) called action potentials to the muscle cells they serve to initiate contraction.
Membrane Potentials
- Resting membrane potential
- Graded potentials and local depolarization
- Action potentials
- Propagation
- Action potential Frequency
Resting Membrane Potential
The nerve cell and muscle cell are like a charged battery ready to do work.
Due to selective permeability properties of the membrane (ions cannot freely cross and therefore unable to reach equilibrium) and active transport by the NA+/K+ pump (pumps 3 Na+ ions out and 2 K+ ions in), a concentration gradient is established and maintained with:
High conc. Of Na+ outside the cell and low conc. Inside.
High conc. Of K+ inside the cell and low conc. Outside
Net result is intercellular environment is more negative than extracellular environment, approximately -70 mV (resting not undergoing potential)
Note: There are other ion and factors that contribute to the resting membrane potential that will not be discussed.
Resting membrane potential can vary from -40mV to -95mV depending on type of cell, but will only use -70 mV neuron.
Graded potentials and local depolarization
A. The electrical signal or impulse, called an action potential can be defined as a reversal in the membrane potential (inside the cell becomes positive).
B.This is achieved through the movement of ions across the membrane
C. Two types of channels:
*Ligand-gated channels: Slower less stuff
Open and close due to presence or absence of a chemical signal called ligand (more specifically, a neurotransmitter) that binds to the receptor site.
Ligand binds -> channel opens
Ligand unbinds or it is not present -> channel closes
Localized to dendrites and cell body of the neuron and NMJ/ motor end plate of muscle fiber
*Volatge-gated channels: Large influx in faster
Open and close response to a change in voltage.
Membrane potential reaches a certain voltage or charge -> channel opens.
Membrane potential reaches a different Volatge or charge -> channel closes
Widely distributed along axon of neurons and sarcolemma of muscle fiber and act much faster compared to ligand -gated channels .
D. When the cell receives a signal (i.e. Neurotransmitter binds its receptor), ligand-gated Na+ channels open and Na+ begins to leak into the cell down its concentration gradient.
This produces a step- wise progression toward a more positive charge, and we call this a local depolarization
The membrane potential moves from -70mV to -69mV, etc.
E. As more and more ligands bind, more and more ligand-gated Na+ channels open, and more and more Na+ leaks into the cell causing further local depolarization.
F. This continuous until threshold is reached, approximately -65mV depolarization (i.e. Movement toward a more positive charge)
All-or-none phenomenon
If threshold is achieved, an action potential is fired. If its not, no action potential takes place and cell returns back to its resting membrane potential.
note: If threshold is achieved, then no more ligand neurotransmitter is necessary and Volatge-gated channels take over. Ligand-gated channels are technically done at this point.
Action Potential
A. The action potential is defined as a reversal of the membrane potential, with a total change in voltage of about 100mV as the membrane potential skyrockets from -70mV to +30mV
B. Two phases (lasting less than one second total):
*Depolarization phase:
At -65mV, and once threshold is achieved, voltage-gated Na+ channels open
Na+ rushes into the sell down its concentration gradient (produces huge influx of Na+), and this produces a rapid depolarization
This continues until membrane potential reaches +30mV
*Repolarization phase
At +30mV, the voltage-gated Na+ channels close and the Volatge-gated K+ channels open.
K+ rushes out of the cell down its concentration gradient (produces huge efflux of K+), and this produces a rapid Repolarization (membrane potential returns to a negative voltage)
This continues until membrane potential reaches -70mV, at which time the voltage-gated K+ channels close and Na+/K+ pumps reestablish concentration gradients
C. Refractory period
Defined as a short period (less than one second) after an action potential has occurred where the cell cannot immediately fire another signal
Direct result of the temporary destruction of concentration gradients in response to the ion movement discussed above, so Na+/K+ pumps must reestablish concentration gradients before another signal can be fired.
Propagation
A. In nerve cells and muscle cells, as an action potential is reached on small sections of a cell’s membrane, they set off other sections of the membrane to pass threshold. It is self-propagating.
B. The action potential moves (propagates) only in one direction, away from the origin of the nerve impulse (much like a domino effect).
C. Net result is that nerve cells release neurotransmitters at their pre synaptic (or axon terminals or muscle cells contract.
Action Potential Frequency
Repeated ligand releases by the stimulating nerve (repeat stimulation) will cause repeated action potentials that can increase strength of a cells response (an increase in strength or duration of contraction in muscle cells).
II. Neuromuscular Junction (also called a “Synapse”)
A. Transfer site of motor neuron action potential to skeletal muscle cell action potential
B. Physiology of the NMJ
A. Transfer site of motor neuron action potential to skeletal muscle cell action potential
Each muscle fiber is stimulated by a terminal branch of an axon
Structures or areas: Presynaptic terminal (also called axon terminal) with synaptic vesicles
Synaptic vesicles: membrane-bound sacs that contain neurotransmitters thousands of them per vesicle)
Acetylcholine (Ach) is the excitatory NT of the NMJ
Synaptic cleft
Postsynaptic membrane or “motor end plate”
B. Physiology of the NMJ
- Action potential propagates down the axon of the motor neuron and arrives at the Presynaptic terminal.
- Voltage change (depolarization) causes voltage-gated Ca2+ channels to open and Ca2+ diffuses inward
- This causes the synaptic vesicles to fuse with the axon membrane and release their neurotransmitter (A Ch) into the synaptic cleft by Exocytosis
- Ach diffuses across the cleft and binds onto its receptor (a ligand-gated Na+ channel) on the post synaptic cell.
- Ligand-gated Na+ channels on the sarcolemma of the muscle fiber open and Na+ diffuses inward.
- This produces a local depolarization in he skeletal muscle fiber, and if enough local depolarizations are achieved to reach threshold, an action potential is initiated.
- Neurotransmitter effects are then terminated
- The binding of the neurotransmitter to its receptor is reversible, and its effects generally last only a few millisecond before being terminated
- ACh is quickly broken down to acetic acid+ choline by an enzyme called acetylcholinesterase (AChE)
- This removal of ACh prevents continued (and most likely undesirable ) muscle fiber contraction in the absence of additional nervous system stimulation.
8. Clinical: cont…
Physiology of the NMJ
8. Clinical
A. Many toxins, drugs, and diseases interfere with events at the NMJ
B. Some target or limit acetylcholinesterase (AChE) activity.
Results in continued stimulation of the muscle fiber (termed spastic paralysis) and eventual muscular fatigue.
Death through respiratory failure. Ex. Organophosphate pesticides and some nerve gases.
C. Others target (either block or damage) ACh receptors.
Doesn’t allow ACh to bind so no muscle fiber stimulation.
Results in flaccid paralysis.
Ex. Snake venom, anesthetics, etc.
D. Myasthenia gravis
Characterized by drooping upper eyelids, difficulty swallowing and talking, generalized muscle weakness.
Involves a shortage of ACh receptors that are thought to be caused by an autoimmune disorder
Although normal number of receptors are initially present, they appear to be destroyed as the disease progresses.
D. Tetanus toxin
Targets regulatory neurons that control release of ACh from Presynaptic motor neurons
Floods cleft with ACh and results in continued stimulation of muscle fiber (synaptic paralysis) and eventful muscular fatigue.
Death through respiratory failure.
E. Botulism toxin
Blocks release of ACh from Presynaptic cell.
Results in flaccid paralysis (no muscle fiber stimulation)
Death through respiratory failure
III. Excitation-Contracting Coupling
A. Sequence of events by which transmission of action potential along sarcolemma leads to sliding of actin and myosin myofilaments
1. Action potential is brief and ends well before any signs of contraction are obvious.
2. The action potential also does not act directly on the myofilaments and instead causes the necessary rise in intracellular calcium ion concentration that is required in order for action and myosin myofilaments to interact and slide.
B. Sequence:
1. Action potential (that was initiated at the NMJ) propagates along the sarcolemma until it reaches the T tubules.
- T-tubule invagination takes the sarcolemma depolarization (AP) into the Sarcoplasmic reticulum (SR)
- Volatge change (depolarization) in the T tubules causes voltage-gated Ca2+ channels in the Sarcoplasmic reticulum to open and massive amounts of Ca2+ diffuse into the Sarcoplasm (all within 1 millisecond).
- Ca2+ then binds to the regulatory protein tropoin, changing its conformation and exposing the myosin binding site on actin for the first time.
- With the myosin binding site on actin now open, myosin binds onto actin through a step called cross bridge, and contraction (cross bridge cycling) begins.
IV. Muscle fiber contraction: cross bridge activity
Muscle fiber contraction (3 steps)
- Cross bridge:
Myosin head engages (binds actin) and myosin are now physically linked. - Power stroke:
Myosin head pivots and bends, pulling the actin over the top of itself and the bare zone narrows. - Recovery stroke (cocking of the myosin head):
At the cost of ATP, the myosin head is dislodged from the actin and returns to its pre stroke high-energy, or “cocked”, position.
If Ca2+ is still available because of continued stimulation, the myosin head reengages. - Through many quick repeats of the cycle, the myosin heads “walk” along the adjacent actin (thin) filaments (much like a centipedes gait) and the Sarcomere shortens and contraction is achieved in each fiber that has been stimulated by the neuron.
The actin filaments cannot slide backwards as the cycle repeats again and again because some of the myosin heads (“legs”) are always in contact with actin (“the ground”).
It is likely that only half of the myosin heads of a thick filament aware pulling at the same instant. The others are randomly seeking their next binding site.
V. Relaxation of muscle fiber (if no more stimulation is present)
A. Sequence
1. Ca2+ ions are rapidly pumped back into the Sarcoplasmic reticulum by active transport (requires ATP).
- ATP is used to dislodge the myosin from the actin and “recock” the myosin heads.
- With free intracellular Ca2+ no longer present, troponin returns back to its original conformation and blocks the myosin binding sites on actin.
- Sarcomeres passively lengthen.
B. Clinical cont.
V. Relaxation of muscle fiber (if no more stimulation is present)
B. Clinical
- Rigor mortis
A. Most muscles begin to stiffen 3 to 4 hours after death with peak rigidity at about 12 hours and that then gradually dissipates over the next 48 to 60 hours.
B. Dying cells are unable to exclude Ca2+, and this influx into muscle cells promotes formation of myosin cross bridges
C. Since ATP synthesis also ceases, cross bridges detachment is impossible.
D. Actin and myosin therefore become irreversibly cross-linked, producing the stiffness of rigor mortis, which gradually disappears as muscle proteins break down after death.
