Excitation Contraction Coupling Flashcards
Describe the structure of the neuromuscular junction
Presynaptic terminal = button has Ca, & Ach
Postsynaptic terminal = endplate has Ach receptors
Describe how the action potential leads either to muscle twitch, summation, tetanus, or treppe
See pg. 259 - 260
The force produced by a single skeletal muscle fiber can be increased by increasing the frequency of stimulation of the fiber.
A single action potential produces 1 twitch.
Increase in muscle tension from successive action potentials is called summation (the tensions from the AP’s add together) and a maintained contraction in response to repetitive stimulation is called tetanus. If a tetanus oscillates, it is called unfused tetanus while a tetanus without oscillations is called fused tetanus.
Repeated stimulation of the muscle at low frequency can produce “treppe”. THIS IS NOT SUMMATION because each twitch relaxes to zero tension before the next twitch initiates (the tensions from the AP’s DO NOT add together). However, in treppe successive twitches show greater peak tension. This occurs in a step-wise fashion hence the phenomenon is called treppe (german for stairs or steps).
Describe a motor unit
A motor unit is one somatic motor neuron and all the muscle fibers (myofibers) it innervates. A single neuron will innervate multiple muscle fibers BUT a single skeletal muscle fiber is innervated by only one neuron.
Generally large motor units are found in fast twitch muscle (Type II) while small motor units are found in slow twitch (Type I) muscle. When a motor unit is activated, all of the innervated muscle fibers are simultaneously stimulated to contract with all-or- none twitches.
Describe the principle of recruitment & the size principle
Motor units are recruited according to the Size Principle. Smaller motor units (few muscle fibers) are recruited to fire first. As more force is required, to lift something heavier, larger motor units are recruited after the smaller ones.
When requirements for force are low, but control demands are high (e.g. writing, performing surgery) the ability to recruit only a few muscle fibers gives the possibility of fine control. As more force is needed the impact of each new motor unit on total force production becomes greater.
Recruitment is the major mechanism for increasing the strength of skeletal muscle contraction. Recruitment involves the activation of more motor neurons that leads to activation of larger numbers of myofibers (muscle cells) within the particular skeletal muscle. As additional myofibers are stimulated, additional tension is produced by the muscle as a whole.
Generally, smaller motor units are composed slow twitch fibers (type 1), while the larger motor units are composed of fast twitch (type 2) fibers.
Describe the respective properties of fast twich glycolytic fibers and their susceptibility to fatigue
Type 2b
White color = low myoglobin
*Fatiguable
Glycolytic metabolism (breaks down glycogen)
Few mitochondria & high glycogen
Describe the respective properties of fast twich oxidative fibers and their susceptibility to fatigue
Type 2a
Red color = High myoglobin
*Fatigue resistant
Oxidative metabolism
high mitochondria & glycogen
Describe the respective properties of slow twich oxidative fibers and their susceptibility to fatigue
Type 1
Red color = High myoglobin
*Fatigue resistant
Oxidative metabolism
high mitochondria & low glycogen
Describe the steps of excitation contraction coupling
- A motor action potential travels along a motoneuron to the motor endplate (presynaptic component) at the neuromuscular junction.
- The nerve endings secrete acetylcholine (Ach) which acts on a local area of the sarcolemma to open numerous NICOTINIC acetylcholine-gated ion channels.
- Opening of these channels permits sodium ions to flow into the muscle, thus depolarizing the muscle membrane potential, and initiating an action potential which propagates along the muscle fiber plasma membrane, called the sarcolemma, in the same way that action potentials propagate along nerve axons.
- The muscle action potential propagates down the sarcolemma invaginated T-tubule (transverse tubule) membranes deep into the interior of the muscle fiber to the triad junction (1 T-tubule & 2 SR), where it causes release of calcium ions that have been sequestered in the longitudinal sarcoplasmic reticulum (SR = a bag of calcium). In other words, depolarization of the T-tubules opens calcium channels, called ryanodine receptors (first in the dihydropyridine receptor and subsequently in the ryanodine receptor), in the sarcoplasmic reticulum (SR), releasing Ca2+ into the sarcoplasm. Note that some calcium is retained & bound to calsequestrin in the SR.
- The increased concentration of calcium ions in the sarcoplasm causes the actin and myosin filaments to interact with each other, resulting in a sliding motion that shortens the length of the sarcomere.
- The calcium ions are then pumped actively back into the sarcoplasmic reticulum (up their gradient) by the Ca-ATPase ion pump located in the sarcoplasmic reticulum membrane, thus reducing the concentration of calcium in the sarcoplasm, and allowing the muscle fiber to RELAX. The sarcoplasmic reticulum calcium ATPase, called SERCA, uses the energy of ATP hydrolysis to pump calcium back into the sarcoplasmic reticulum.
- Lengthening of the muscle is achieved by contraction of an antagonistic muscle, e.g. contraction of the triceps lengthens the biceps.
Describe the events @ the neuromuscular junction for muscle contraction and the role of cholinergic transmission in endplate potentials
1) The NEURONAL action potential travels down the motor neuron axon in a saltatory (leaping) fashion between nodes of Ranvier in myelin sheath. The NEURONAL action potential travels to the terminal button (or bouton) which can also be called the presynaptic terminal.
2) The NEURONAL action potential depolarizes the terminal bouton and this causes the voltage-gated calcium channels in the plasma membrane of the bouton to open. This allows calcium ions to rush into the bouton.
3) Elevated calcium within the terminal bouton of the motor neuron causes the vesicles of acetylcholine neurotransmitter to fuse with the membrane and dump their contents into the synaptic cleft. The cleft is the space between the terminal bouton and the motor end plate.
4) Acetylcholine binds the NICOTINIC Acetylcholine receptors embedded in the MUSCLE plasma membrane (at the motor endplate).
5) The Acetylcholine receptors then open, allowing sodium (Na+) to rush into the muscle cell and depolarize the motor endplate. This produces a change in the endplate potential. Some potassium (K+) can also come out of the cells through the open Acetylcholine receptor. Note that depolarization induced by the opening of nicotinic acetylcholine receptors in the endplate causes the opening of voltage gated sodium channels in the plasma membrane around the endplate.
6) The depolarized endplate potential causes nearby adjacent voltage-gated sodium channels in the MUSCLE plasma membrane to open leading to the initiation of a MUSCLE action potential that propagates down the length of the muscle fiber (bidirectionally) away from the synaptic cleft.
7) Acetylcholinesterase quickly inactivates the released acetylcholine.
Myasthenia Gravis
In myasthenia gravis, an autoimmune disease, antibodies block or reduce the number of nicotinic acetylcholine receptors at the neuromuscular junction, resulting in muscle fatigability.
Edrophonium chloride is a acetylcholinesterase inhibitor, and thus increases acetylcholine at the neuromuscular junction by decreasing acetylcholine breakdown at the neuromuscular junction. This will will temporarily relieve symptoms of muscle weakness.
Describe the difference between small & large motor units
Small motor units are involved in fine motor control, for example in fingers and eyes
Larger motor units are involved in coarser movements. Skeletal muscles produce more force when more (and larger) motor units are recruited.
What are the 2 mechanisms for regulating muscle contraction?
1) Recruitment (most important)
2) AP rate coding & summation
Tetrodotoxin (TTX), is a toxin that blocks voltage gated sodium channels. Where could TTX act to block excitation contraction coupling?
In the motor neuron axon & in the sarcolemma
TTX works both in neurons & in the muscle
3 mechanisms of muscle relaxation
Skeletal muscle contraction is terminated by the removal of calcium from the sarcoplasm, which is an ACTIVE PROCESS.
The major mechanism for calcium removal involves the sarcoplasmic reticulum calcium ATPase (SERCA). SERCA 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.
There are two other mechanisms of calcium removal from the sarcoplasm that do extrude calcium into the extracellular fluid (outside the cell). The first is called the plasma membrane calcium ATPase or PMCA that uses the energy of ATP hydrolysis to remove calcium from the sarcoplasm. PCMA pumps 1 calcium ion out of the cell at the expense of 1 ATP molecule.
The second mechanism is the Sodium Calcium eXchanger (NCX). NCX lets 3 sodium ions into the cell (down the Na+ gradient) to remove 1 calcium ion from the cell (up its gradient).
Summation & tetanus cannot occur when
The AP refractory period duration is very long compared to the twitch duration. This is the case in cardiac muscle so summation doesn’t occur.
The opposite is true in skeletal muscle so that summation can occur.