Muscle physio Flashcards
What are the proteins in the Sarcomere?
Titin: The largest protein of the body. Contains one spring-like protein chain. It originates form Z-lines and ends at myosin bundles. Titin ensures a precise return of actin and myosin bundles to their original position.
Nebulin: determine the direct and placement of actin polymerization during the developemt of the Sarcomere. It protects the developed actin fibre form rearranging effect of other actin-binding proteins.
Alpha-actinin: Creates the Z-band. Is a net-like protein. Provides a binding site for the actin complexes orienting toward the inner part of the sarcomere.
What is a G-actin?
It is the main component of the actin-complex. It forms polarized actin-fibres winding up as double helix.
What is Tropomyosin?
Exisits on the surface of the helix. In resting state, it covers active sites (Amino Acid Sequences) on the surface of actin molecule which could stimulate ATPase activity of myosin.
What is Masking?
It takes place when a complex protein, troponin-complex, binds to tropomyosin.
Tn-I (ihibitory) and Tn-T (tropomyosin bining) parts of troponin complex holding tropomyosin in position.
Tn-C (calcium-binding) part is calcium free in resting condition.
How is Tn-C activated?
After calcium binding and through conformation changes it displaces tropomyosin fibre. Tropomyosin then slides into the groove of the two stranded actin helix and prevoisuly masked myosin-binding (ATPase) amino acid sequences become uncovered on the surface of the actin. Cross-bridge cycle starts.
What do the myosin consist of?
6 elementary myosin molecules. Two heavy chains (HC) are composed of an elongated alpha-helix and a globular part. The globular part forms the head of the myosin (cross-bridge) which has an angle of 90* with the alpha helicec. There are two light chains (LC) connecteed to the head regions of both alpha-helicec. The LC has ATPase activity.
Function of the Myosin
The head region may bend with a maximal angle of 45*- this part contains chanis responsible for ATP binding and slitting (myosin isotipes).
Three types of ATPase occur: LC-1, LC-2 (in fast-twich type) and LC-3 (in slow-twich type).
Explain the sliding filament mechanism
The fundamental process is the shifting of myosin head by 45* which occurs after the development of connections between myosin head and actin microfilament. This event has a very short time, but it has several steps:
1: Calcium ions bind to Tn-C´s, then tropomyosin molecules will move.
2: Actin and myosin bind to each other, ATPase is activated, sliding occurs and connection between actin and myosin is releases.
3: myosin head binds ATP and will berepositioned toits original conformation.
If Ca2+ is present, then a new cycle takes place. If IC calcium-signal is terminated, the cross-bridge cylce stops.
What is the Asynchronous cylces?
it results in the apporoaching of Z-bands to each other, and results in the shortening of the sarcomere length and the muscle itself.
This also means that the Myosin filament cant “fall back” - > continous contraction.
Explain the Cross-bridge Cycle
The initial step is the development of Calcium signal. Calcium is released from the sarcoplasmic reticulum after neural AP is transmitted to the muscle. (explain calcium transient). As an effect of calcium ions, actin-myosin connection is formed. Actin activates myosin, which (due to its ATPase activity) splits the boud ATP and energy is released. With that energy myosin head moves, and because it binds actin Z-lines also moves towards the center of the sarcomere (= contraction).
What is Calcium transient and where does it happen?
It happens in the Cross-Bridge cycle. Calcium is released from the sarcoplasmic reticulum after neural AP is transmitted to the muscle. Concentration of calcium in the intracytoplasmic space is 1000 times increased. Rising Ca2+ levels triggers a number of Calcium Re-pumping mechanisms, which result in down regulation of the calcium increase (leading to Ca2+ elimination from the cytoplasm). Therefore Ca2+ conc. near the sarcomere falls down to the micromolar level again = this is called the calcium transient.
The following events of muscle contraction (after cross-bridge cycle) depends on?
The presence of ATP in the system.
If there is no more ATP in the system: Actin binds myosin heads (in 45*) by myosin cannot dissociate from actin and muscle enters a sustained, inactive, contractile state. this happens when ATP stores exhaust after death and muscle spasm happens (=rigor mortis).
And they depend on the availability of calcium! (explain)
The function of calcium in the event of muscle contraction:
If calcium is present: the cycle restarts again and again. If there is no calcium present, tropomyosin slides over the myosin activating part of actin and the muscle relaxes. In this case myosin heads bind ATP, become rich in energy and form a 90* angle with the longitudinal axis of myosin molecules.
ATP related conformational changes at cross-bridge cycle
Step 1:
F-actin and tropomyosin.
Basic situation = myosin head (cross-bridge) is charged.
90*
Relaxation, Resting
ATP related conformational changes at cross-bridge cycle
Step 2:
Ca, ADP, Pi..
AP result in Ca realease, TnC-Ca pulls of Tropomyosin, myosin binding sites are now available. Cross bridge binds to Actin, energy deliberated. = Power-stroke-1… 40*
Power-stroke 2= ADP dissociation resulting in furhter deliberation. 45*
End result is contraction = lowest energy status.
ATP related conformational changes at cross-bridge cycle
Step 3:
If ATP is present - head binds ATP again. Energy is deliberated, therefore the head is back to 90*, this is the “cocked head” status (rich in energy).
In the same time Ca is removed therefore Actin and Myosin are detached.
Relaxation = te highest energy saturation.
Explain electro-mechanical coupling
Neural action potenital is transferred to the muscle fibre at the myoneural junction area, resulting in a propagating AP on the myolemma. The electrical signal of the myolemma finally reaches the triad through the system of T-tubuli, where it is transformed into the calcium-signal. This triggers the mechanical response of the muscle = contraction occurs.
Explain the steps in electromechanical coupling:
- Action potential reaches the myolemma from the NMJ.
2: AP reaches the L-type (voltage gated) Ca2+-channels in the T-tubuli, the L-type channel open.
3: Because the L-channels open, the ryanoid-Ca2+ will also open.
4: From the sarcoplasmic reticulum (SR) a lot of Ca2+ will get into the IC part of the cell.
5: the Ca2+-channels on the myolemma will also open (Ca2+ influx from the EC).
6: result = IC Ca2+ level will be really high around the sarcomer
Explain the steps of Electromechanical coupling from AP to contraction
- Ca release thorugh the funtion of the TRIAD (T-tubules + two SR terminal cystern.
2: Activation of muscle proteins (Ca initiates the connection between Tropomyosin- Tn complex leading to the formation of Acto-myosin complex).
3: Muscle contraction. If Ca is available there will be continuous power strokes of cross bridges creating contraction through “walk-along” mechanism.
4: Relaxation. Follows the process (Ca elimination from IC space either:
a) Na/Ca antiport mechanism (to the EC space)
b) ATP dependent Ca-pump to the SR
c) And/or to other compartments (i.e mitochondria)
What are the potential dependent Ca-channels in T-tubul membrane:
L-type sensors (channel): which can be blocked by dihydropyridine, DHP.
T-type (ryanoid) Calcium channels: which open/close depending on their conformational state.
What is the morphological basis of the excitation-concentration coupling?
The triad
What happens in the Triad?
this is where T-tubule of he myolemma is closest to the IC sarcoplasmic reticulum. As an effect of the AP, the conformation of T-tubule voltage-sensing receptor (DHP or L-type calcium channel) is changed. This opens the T-type ryanodin calcium channel on the SR membrane: a high amount of Ca2+ is released from the RS into the intracytoplasmic space.
Thorugh a positive feedback, Ca opens the rest of the SR ca channels. All these result the increase of calcium-concentration which triggers the cross-bridge cycling.
The removal of Calcium from the cytosol
- Sodium/calcium ion antiporter between myolemma/EC spaces removing calcium with a secondary active transport mechanism.
2: Active calcium pumping to the SR by active ATP dependent calcium pump.
3: other sequesters (organelles compartmentalizing calcium feks mitochondria or small vesicles.
Chemical composition of muscle tissue:
Water: 75%
Protein: 20%
- Structural proteins (contrctile 50%, other 20%)
- soluble proteins (albumin 20%, enzymes 10%).
Other: 5%
- ATP mmol/kg (skeletal muscle 5, cardiac muscle 1.5, smooth muscle 2).
- Creatine phosphate mmol/kg (skeletal 20, cardaic 2, smooth 0.7).
Types of striated/skeletal muscle:
Pink, white and/or red.
Phasic type- fast twitch muscle fiber:
Pink and white muscle types
Tonic type- slow twitch muscle fiber:
Red muscle type.
Characteristics of Pink muscle types:
ATPase type: fast SR pump: fast Junction/fibre: 1:1 T-system: developed Muscle AP/neural AP: exists/very frequent. contrac. time m/s: 20 Metabolism: mixed Fatigue: slow Fibre length: intermediate
Characteristics of White muscle type:
ATPase type: fast SR pump: fast Junction/fibre: 1:1 T-system: very developed Muscle AP/neural AP: exists/very frequent. contrac. time m/s: 10 Metabolism: Anaerobic Fatigue: Fast Fibre length: very long
Characteristics of Red muscle type:
ATPase type: slow SR pump: slow Junction/fibre: "en grappe"-type T-system: not developed Muscle AP/neural AP: no/rare contrac. time m/s: 200 Metabolism: Oxidative Fatigue: No Fibre length: very short
Muscle hypertrophy
Involes an increase in seize of skeletal muscle through a growth in size of its component cells.
Two factors that contribute to hypertrophy:
- Sarcoplasmic hypertrophy, which focuses on increased muscle glycogen storage.
- myofibrillar hypertrophy which focuses on increased myofibril size.
Energy source of muscle functioning
- Both contraction + relaxation need ATP:
ATP concentration of myocyte 5mmol/l, covers the oxygen need for 2-3sek. - Concentration of Myocyte CRP: 20mmol/l, energy supply for 20-30 sek.
Energy source for Anaerob glycolysis - muscle functioning can be:
- Glycogen: for fast movement, glycogenolysis.
- Glucose: for prolonged, long term contraction.
- Anaerob glycolysis: during heavy physical activity
the source is glucose, the end-product: Lactic acid, through piruvate.
Oxygen dept
Energy sources for Oxidative Phosphorlation of muscle functioning can be:
- Pyruvate is transformed to AcCoa (and not to lactate)
- Produces 36 ATP and CO2
- Energy source of very long-term muscle activity
No oxygen dept.
What will happen to the muscles that cover most of their energy needs by anaerobic glycolysis?
They will resynthesize previously depleted energy stores after work: in this phase resynthesis is going under Aerobic conditions. Muscles shows increased oxygen consumption.
What are the elements of macroscopic investigation of muscle function?
- Elements of Contraction (Contracting Component) CC = Sarcomer.
- Elastic elements (SEC; serial elastic components, PEC; parallel to tendons)
Types of contraction:
- Twitch
- Isotonic contraction (constant tension, regular physiological activity)
- Isometric contraction (tension is changed, but not the length)
- Auxotonic: working against increasing tension, resistance
- Preload: muscle length is adjusted with (pre)load, then isotonic contraction.
- Afterload: contraction begins with isotoic, then blocking of contraction with a load.
Twitch
To an appropriate stimulus muscle answers with contraction: a muscle twitch occurs. After the arrival of AP myoplasmatic reticulum calcium concentration increases, contraction takes place.
Elements (macroscopic examination of muscle function)
During stimulation, due to the contraction of CC, first the SEC elements will reach equilibrium with the load (only the tension is increased). followed by shortening with constant tension.
Isotonic contraction
Muscle shortens with constant tension
Isometric contraction
When only tension is changed but not the length of the muscle.
All or none law
Applies for single fiber only (myocyte). Adequate stimulus (treshold) causes maximal contraction. Inadequate stimulus (below treshold) - no contraction. The amplitude of contraction does not change with the streght of stimulus - contraction is always the same.
Quantal (motor unit) summation:
in a given muscle more and more fibers re contracted due to increased frequency of AP, even the fibers with increased-treshold are contracting.
Contraction (frequency) summation:
in case of repetitive stimulu (increased frequency of AP) there will be additional Ca release before the end of Ca transient. The result is increased amplitudes of contraction, due to extra Ca release, while Ca is still present.
Staircase effect:
(warming up) if new stimuli arrive immediately after the end of the twitch, the new contractions have increasing amplitudes. the reason: increasing efficiency of the ion gated. frequency of AP does not change the reason is the summation of remaining Ca.
Tentaus:
Additive effect. extremely increased frequency of stimuli - two forms: incomplete, then complete tetanus. extreme ca release.
When can length-tension curve be obtained?
when one stimulates (with maximal single impulse) muscles, which are passively stretched with varying loads.
How can we construct the area where muscles execute normal physical work?
As a result of Isometric, Isotonic, Preload and afterload experiments.
Work=
Length x Tension (load)
How can you obtain the Isotonic maximum curve in length-tension diagram?
If we passively stretch the muscle to distances above resting length (Lo) and in these positions we stimulate the muscle with maximal single stimuli.
How can you obtain the Isometric maximum curve in length-tension diagram?
No shortening is possible here, so we can only measure the extent of tension
Velocity/tension relationship (power):
Direct relationship between velocity of shortening and tension-parameters of muscle contraction.
- the less the tension is, the higher the veloity becomes.
- the heavier the load is, the slower the peed of lifting becomes.
Power=
Velocity x tension
What values varied of the velocity of shortening?
- unloaded muscle contracts with maximal velocity (Y intersection)
- overloaded muscle contracts with zero velocity (X intersection)
What does different power values belonging to actual tension and velocity parameters show?
That intermediate tension and intermediate velocity result in maximal power.
Power values of skeletal muscle:
maximal tension: 3-6 kg/cm2 maximal speed: 7 m/sec Total force: 200 N Efficiency: 20% Power maximum: - short temr: 3-5000 W - long term: 1200 W
Heat production during contraction:
ATP breakdown
Heat production after contraction:
Synthetic processes create heat.
Heat production of Phasic (fast, white) fibers:
Produce more heat during restitution! During contraction the energy is provided by anerob glykolysis - resulting in high o2 dept - which must be replaced during restitution (which means resynthesis of ATP in the presence of O2)
Heat production of Tonic (slow, red) fibers:
Heat production mostly occurs during contraction.
Phases of Heat production:
- In resting
- Initial heat
a) activation
b) contraction - Restitution heat
Heat production in resting:
The maintenance of muscle tonicity generates HEAT - that creates most of the BMR (Basal Metabolic Rate)
Heat production in Initial heat:
Production is related to the 4 phases of electromechanical coupling:
a) Activation Heat: connected to the first 2 phases (1, Ca-release + 2, Myosin-activation)
b) Contraction Heat: last 2 phases (3, sliding filament mechanism + 4, Ca re-pumping during relaxation)
Heat production during Restitution Heat:
characteristic mostly to phasic (fast ,white, anaerov-glytolytic) muscles.
The huge O2-dept, created during contraction, must be replaced by ATP resynthesis during RESTITUTION, which generates heat.
Fatigue of the muscle depends on?
the ratio of Phasic (fast) and Tonic (oxydative) fibers
In Vitro fatigue:
a) lack of =2 (muscle stimulation in N2 rich environment: the result is unrecoverable fatigue.
b) lack of transmitter (occurs only in experimental conditions + in special diseases)
In Vivo Fatigue:
a) Peripheral: decrease of energy sources -> increase of metabolic by-products -> lactic acid (direct blocking of contraction due to protein denaturation)
b) central fatigue: exhaustion of motor-unit (due to lack of vesiculum production of motoneuron)
exhaustion of myoneural junction.
Subjective feelings of Fatigue:
due to:
- increased heat production
- decrease of pH
- direct effect of Lactic Acid
- dehydration
- General hypoglycaemia
Signs of Fatigue on Mechanogram:
a) decreased amplitude of contrction
b) prolonged contraction (slow relax.)
Fatigue develops earliest in?
Fast (glycolytic, phasic) fibers than in tonic (oxidative) muscles.
How is the AP generated on the myolemma?
if it is stimulated through the nerve.
Where does the transmission of neural action potential to the muscle takes place?
in the area of the myoneural junction (muscle-nerve connection)
What is the essence of the muscle-nerve connection/myoneural junction
It is the Acetylcholine release induced by the AP at the nerve terminals. This chemical signal binds to the nicotinic receptors of the muscle membrane and results in the opening of ligand activated cationic channels.
What happens when the Cationic channes are opened?
It produces a local current (end plate potential, EPP) which is decrementally conducted to the fast, voltage gated sodium channels, situated next to the myoneural junction.
There, a sudden conformation change is induced and then AP is formed in the myolemma (muscle membrane)
Regulation of Muscle function: Steps of AcChol Production:
- synthesis of vesicles (=40 nm) in the Golgi of motoneuron.
- “flow” of vesicles toward the axon know (300K vesic/End plate)
- Synthesis of AcCh in the cytosol: immidiate transport to vesicles (10K AcCh/vesicle is produces: one AP result in 150-300 vesicles exocytosis)
- AP running through the axon - opens up Voltage Gated Ca channels, Ca influx from EC space increases Ca-concentration 100x in the knob, and initiates AcChol containing vesicles exocytosis.
- AcCh gets into the synaptic space:
a) a small portion of it disappears by diffusion
b) non-R-bound is catabolized
c) most of the AcCh are bound to AcCh-receptor (Ach-R) - Creation of Miniature-EPP (MEPP) on the myolemma by AcCh: in resing 1-2 vesicles open up, the small amount of AcCh creates 1 mV MEPP, which lasts only for few msec (not enough to generate AP!)
- Extensive exocytosis results in the lack of vesicles - these vesiculum related membrane pieces may return later to cytosol thorugh endocytosis and will be refilled with AcCholine agian!
What is Acetylcholines role in the Neuromuscular junction?
It is the neurotransmitter used at the neuromuscular junction - in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles.
What is the role of Clathrin?
The mechanism of endocytosis is stimulated by clathrin (which is a contractive protein, attached to the inner membrane).
To bring something from the putside of the cell inside, clathrin molecules combined at the cell emmbrane to form a clathrin-coated pit on the inside surface of the outer cell membrane. The pit then rounds and pinches off, trapping a section of membrane in a clathrin-coated vesicle.
Muscle-type acetylcholine receptor is a…?
ligand gated receptor with three possible conductance states: 1. closed, 2. open, 3. inactivated
What makes the blocking effect of curare and bungarotoxin?
Muscle-type nicotinic acetylcholine receptor molecule is composed of two alpha, two beta and one delta subunits. This structure makes possible the competitive blocking effect .
What happens when the Ligand binding to the acethylcholine receptor?
It opens cation channels and end-plate potential (EPP) is generated. It is conducted with decrement ot the neighbouring voltage gated sodium channel and action potential is generated. Acetylcholine may cause a 100 mV EFF when released in high concentration. Decremental conduction of it is enough to pass the treshold potential of the neighboring voltage gated sodium channels.
What is Decremental Conduction?
The signal strengt decreases with the distance traveled.
What happens it there is a increase in EC magnesium concentration?
Antagonize acetylcholine receptor and blocks functioning of the sarcomere.
When and where is increase in EC magnesium concentration important?
in the case of the cattle, where extremely high calcium secretion into the milk after calving decreases plasma calcium level: Mg concentration will not increase, but its higher proportion to calcium results in the same effect as an absolute increase of the Mg concentration: muscles will relax: parturient paresis happens.
The physiological signal transmission in the motor unit:
Action potential from axon -> Calcium enters from the EC, Ach vesicle releases -> Filling up with ACh -> Ach binds to the plasmamebrane receptor -> End Plate Potential (EPP) is generated -> Action Potential (AP) is generated on the myolemma, calcium influx, concentration.
Drugs of AcCh-like action affectng Neuromuscular transmission:
Nicotine (+methacholine), same effect like AcCh, but it can not be degraded by Cholinestrease. Therefore its concentration is increased, and the result is permanent depolarization - contraction lasts through minutes, hours -> intensive spasms.
Drugs of Cholinesterase Inactivators action affecting Neuromuscular transmission:
AcCh is not hydrolyzed, therefore extreme AcCh cumulations occurs (neostigmin, ezerin, nerve gas) -> repetitively stimulate muscle fibers -> spasms, for hours, Laryngeal spasms (lethal)
Curariform drugs action affecting Neuromuscular transmission:
AcCh-R is competitively blocked (AcCh driven Na-channels can not open sufficiently) - therefore: no depolarization -> no contraction, Paresis
Blocking the AcCh release action affecting Neuromuscular transmission:
Botulin Toxin; there will be no contraction -> paresis
Myasthenia Gravis action affecting Neuromuscular transmission:
Autoimmune disease -> AcCh-R blocking auto-antibodies- AcCh can not be bound to the receptor, therefore -> no signal transmission - Paresis
Fatigye of Myoneural Juction action affecting Neuromuscular transmission:
In vivo it rarely happens (extreme exhaust). Experimentally: lack of AcCh synthesis - no signal transmission.
From neural activation to muscle contraction:
- AP of a motorneuron is generated which runs to the myoneural junction.
- ACh containing vesicles open up at the synaptic knobs -ACh deliberation.
- ACh attached to the ACh-R of sarcolemma, then ACh channel opens up.
- Na+ enters through the channels to inner surface; and local EPP is generated, then AP is generated.
- Spreading of AP (in phasic muscle)
- AP activates SR through T-system. Result: Ca2+ is released to the sarcoplasma.
7: Ca2+ initiates Actin-Myosin contraction (sliding filament mechanism). - Finally repumping of Ca2+ into
a) SR
b) Mitochondrium
c) EC
leading to relaxation.
What is is a motor unit?
A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated by that motor neurons axon terminals. Groups of motor units often work together to coordinate the contractions of a single muscle.
What type of motor units do we have?
Large motor unit: Phasic - white. Small motor unit: Tonic- red
What do the Fusimotor system consist of?
Modified muscle fibers in skeletal muscles play a role in stretch-detection (receptor function) and in fine tuning of muscle tension. These specialized fibers (intrafusal fibers) are located among the working fibers (extrafusalfibers)
We can find receptors in tendons called Golgi tendon receptor organs.
What is Fusimotor system- Afferentation?
Information from the fusimotor system to the nervous system. Consists of
- Static fibers: are sensitive to static changes of tension (length) and
- Dinamic fibers: are sensitive to dinamic changes of tension (length and velocity)
The steps of Fine-Tuning of muscle tension:
- Stretching of muscle stimulates muscle spindles.
- Activation of sensory neuron
- Information processing at motor neuron
- Activation of motor neuron
- Contraction of muscle.
Principle of Myotatic reflex?
The efferentation returns to the same muscle where the afferentation is coming from.
Principle of Protective reflex?
Against extra stretch.
What is Co-Activation
Motor command of the cerebral center simutaneously stimulates both alpha and y-motorneurons, which is called co-activation.
If the contraction is appropriately executed, both intrafusal and extrafusal fibers contract with the same rate and strength.
The mechanism rapidly corrects any error in motor command execution
What happens in case of suddenly increased load in Co-Activation?
In case of suddenly increased loasd, the tension in extrafusal fiber is stronger than in the intrafusal.
This is followed by the acceleration of AP frequencies in Ia and II afferents, which will locally adjust the tension of extrafusal fibers (fine tuning)
what are the two major groups of Smooth muscles?
- Multi-unit: individual fibres ar enot connected with gap junctions. Single-, or small groups of fibers are under direct neural control. This kind of smooth muscle is capable of fast and accurate movements (inside of the eye)
- Single-unit: consists of many hundreds of fibers connected with gap junctions and forming a functional syntytium. these fibers are innervated by varicosities. Smooth muscles or vessels or luminal organs are innervated like this.
What features causes the muscle fiber to contract? smooth muscle
The dense bodies and intermediate filaments are networked through the sarcoplasm, causes the muscle fiber to contract
Steps of muscle contraction in smooth muscle:
- Activation of sliding filaments is triggered by MLCK enzyme, if intracellular calcium level is appropriately high.
- Actomyosin complex formation.
- Contraction stays continous until relaxation is triggered by antoher enzyme, MP. If this enzyme is active, a phosphate group is hydrolyzed from actomyosin, myosin and actin separates, muscle relaxes.
- This process is NOT based on the “all or none law”. they are in a weak, but continous contraction.
Basics of smooth muscle:
- Poor blood supply.
- Small, spindle shaped cells.
- Non-striated.
- Non-regular myofilaments.
- Intermediate filaments and dense bodies.
- No transversal tubulary system.
- Small sarcoplasmic reticulum.
The role of Ca2+ in the smooth muscle:
When Ca2+ is available: it binds to the Calmodulin-Ca2+ complex, and it removes the Tropomyosin from binding sites.
If there is no Ca2+: Caldesmon keeps Tropomyosin on binding sites.
What is the subunits of MLC
P-LCh: if non-phosphorilated, it can bind Actin
P-LCh: if phosphorilated, it can bind Actin and contraction will happen
What happens when MLCK is active or inactive?
MLCK inactive: If there is no Ca2+
MLCK active: if Ca2+ is available. P-LCh is phosphorilated, activating Myosin-ATPase, now it binds actin. Only 1 APT is needed.
What happens if we eliminate Ca2+ in the smooth muscle?
Activates Myosin Phosphoatse (MP) - dephosphorilates regulatory P-Lch (ADP + P). Detachment causes relaxation (and in the same time Caldesmon helps Tropomyosin to block actin binding sites aigain) Very slow!
Characteristics of smooth muscle contraction
- prolonged tonic contractions (hours, days)
- Lower frequency of cross-bridge cycles (reason: lower ATPase activity - slower ATP catabolism - slower Myosin head power-stroke)
- Energetically economic
- Lengt contraction 30x longer than skeletal muscle.
What is varocities:
A series of axon-like swelling, called varosities or “boutons”, from autonomic neurons form motor units thorugh the msooth muscle. The Varicosity =/= the axon terminal
Characteristics of Multy Unit (smooth muscle)
- Individual fibers
- No Gap junctions
- Individual innervation
- Contraction is independent in each fiber, and stimulated by nerves - but not through AP.
- transmitters cause local depolarization
- Innervate individual cells.
- Fibers are insulated by collagen and glycoproriten
Characteristics of Single Unit (smooth muscle)
- Hundreds of millions of fibers contractiong all at once, creating a functional syncitium
- lots of gap junctions
- fast penetration of ions
- fast spreading of AP
Sources of Ca2+?
Minor source: SR
Major source: EC-space
What can be found in the myolemma?
Voltage gated Ca2+-channels and many Ligand gated Ca-channels
Types of AP in the Smooth muscle?
AP occurs exclusively in Single-unit. RMP= -50, -60 mV
a) Typical peak potential: initiated by electric stimuli, hormones, generated spontaneously (pacemaker)
b) AP with “Plato”: Extremely prolonged Repolarization. Never makes tetanic contraction.
Factors causing contraction:
Smooth muscle
Smooth muscle contraction functions under very intensive humoral and metabolic regulation
- Spreading of sympathetic (alpha1) or parasympathetic (mACh) neural AP to the myolemma and its effect on voltage gated ion channel (Result: Calcium influx)
- Binding of chemical ligands to ligand gated calcium channels.
- Intracellular IP3 release and G-protein or phospholipase C (PLC) mediated, ligand gated, calcium influc from SR or from Calcium sequester vesicle.
Relaxation of smooth muscle?
Is enhanced by every stimulus which can increase IC cAMP or cGMP level; these also derease IC calcium concentration. Phosphorylation of MLCK or enhanced MP activity also facilitate relaxation.
What are the most important signals of Smooth muscle AP?
Sympathetic beta2 receptros agonists (epinephrine, VIP) also the NO (direct, or diffusivble from capillary endothelia) and, presumably, ATP (act on purinergic receptors)
Local chemical factors incluencing smooth muscle contraction:
- Lack of O2
- Excess CO2
- Increased H+
- Increased Lactic Acid level
- Increased K+
What is the Bayliss effect of smooth muscle (single unit)?
Extension (stretching) of certain smooth muscle results in conraction. This is called the Bayliss effect. It is the self-reflection (myogen response) of smooth muscle, unrelated to neural or hormonal influences.
Mechanism of Myogen response of single Unit muscles:
Stretching effects open up the mechano-sensitive cation-channels creating depolarization. The mechanism (myogen response) takes place in the wall of blood vessels, and has a major role in the regulation of blood circulation (i.e nephron level)
Spontaneous generation of smooth muscle AP
Slow Wate rhytm: Some smooth muscle are self-evcitatory (ie. gut). It is not an AP, but a local potential, if it increases above -35 mV, it initiates AP.
Each slow wave initiates more than one AP promoting a series of rhytmical contraction (called pacemaker waves).
