Basic physiology of muscles

Question 1

What are the 3 types of muscles present in the human body?

Answer 1

• skeletal
• cardiac
• smooth

Question 2

What are some features of skeletal muscle?

Answer 2

• 10-180 micrometres in diameter
• Each fibre extends the entire length of the muscle, usually innervated by one nerve ending
• Thin membrane enclosing a skeletal muscle fibre – sarcolemma
• It consists of the true cell membrane (plasma membrane) and an outer coat made up of thin layer of polysaccharide material containing numerous collagen fibrils.
• At each end of muscle fibre, the surface layer of sarcolemma fuses with a tendon fibre.
• Tendon fibres collect into bundles to form the muscle tendons which connect muscles to bones.
• Intracellular fluid between myofibrils- sarcoplasm Contains large quantities of K, Mg, Pi, enzymes.
• Mitochondria abundant (ATP synthesis)
• Sarcoplasmic reticulum-specialized endoplasmic reticulum of skeletal muscle (calcium storage and release

Question 3

How are thick and thin filaments arranged in one sarcomere?

Answer 3

• each muscle fibre contains several hundred to several thousand myofibrils
• each myofibril is composed of 1500 adjacent myosin filaments and 3000 actin filaments
• thick = myosin
• thin = actin

Question 4

how is a muscle fibre arranged?

Answer 4

muscle fibre >100-1000 myofibrils > 1500 myosin + 3000 actin

Question 5

how is the sarcoplasmic reticulum arranged?

Answer 5

The sarcoplasmic reticulum is arranged as a repeating series of networks around the myofibrils extending from one A-I junction to the next, where they meet is termed the terminal cisterna. They act as reservoirs for Ca2+. Mitonchondria are also present to provide the energy for muscle contraction.
The plasma membrane invaginates transversely forming a tubular system, T tubules, between the cisternae. They contain voltage-sensor proteins which are activated when the membrane depolarises inducing the sarcoplasmic reticulum to release Ca2+. the T tubules and the adjacent cisternae form a triad.

Question 6

What are the functional stages of the sarcomere

Answer 6

• resting stage, with some overlap of the thin and thick filaments
• contracted stage, with an increase in the overlap of the filaments (concentric contraction)
• stretched stage where the thick and thin filaments do not interact (eccentric contraction)

Question 7

what is the structure of thick and thin filaments?

Answer 7

• myosin has 6 polypeptide chains, 2 heavy and 4 light
• F actin, the backbone is a F actin protein molecule (2 in a helix) Troponin is intermittently attached - Troponin T, I, C (loosely bound protein subunits)

Question 8

What causes skeletal muscle contraction?

Answer 8

• the neuromuscular junction is an integral part of the motor unit that comprises a motor neurone and the muscle fibres it innervates
• acetylcholine is the transmitter responsible for generating an end plate potential in the muscle fibres

Question 9

what is innervation and excitation

Answer 9

1. An action potential travels along a motor nerve to its endings on muscle fibres.
2. At each ending, acetylcholine is released
3. Acetylcholine opens Ach gated cation channels
4. Large quantities of Na+ diffuse to the interior of the muscle fibre membrane causing depolarization that in turn leads to opening of voltage-gated sodium channels. This initiates an action potential at the membrane.
5. Action potential travels along the muscle fibre membrane in the same way as along nerve fibre membranes.
6. Action potential depolarizes the muscle membrane, much of the action potential electricity flows through the fibre centre.
   Causes sarcoplasmic reticulum to release large Ca2+ quantity.

Question 10

How does Ca2+ function?

Answer 10

• the gates in the sarcoplasmic reticulum open and the calcium diffuses into the cytosol
• Ca2+ is released into the sarcoplasm and binds to the troponin complex causing changes in the tropomyosin allowing the myosin head to attach and thus contraction is initiated

Question 11

What is the contraction cycle?

Answer 11

Shortening of a muscle involves rapid contraction cycles that move the thin filament along the thick filament
5 stages:
1. Attachment - the myosin head is tightly bound to the actin molecule of the thin filament (rigor state)
2. Release - ATP binds to the myosin head and induces the release from the actin therefore without ATP the muscle would remain in a state of rigour. The muscle is now relaxed
3. Bending
The ATP causes further changes to the myosin head causing it to bend. The bending movement initiates the breakdown of ATP to ADP+inorganic phosphate both of which remain in the myosin head
4. The myosin head binds to the new site and the inorganic phosphate is released. The effects are twofold:
- it increases binding affinity of the myosin for the actin
- the myosin head generates a force to straighten up and in doing so forces the thin filament along the thick filament creating the power stroke and shortening the sarcomere. During this stage the ADP is lost from the myosin head
5. the release of the ADP results in the reattachment of the myosin head to the actin filament and the rigour state is re-established

Question 12

What is relaxation?

Answer 12

• the first step in skeletal muscle relaxation is the cessation of the nerve signal. Ach is recycled by being resorbed into the synaptic knob.
  Active transport pumps in the sarcoplasmic reticulum begins to pump the Ca2+ from the cytosol back into the cisternae. Decreases in Ca2+ causes Ca2+ to unbind from the troponin allowing the tropomyosin to recover the binding sites and therefore myosin can no longer bind to the actin. Tension is no longer produced or maintained

Question 13

excitation-contraction in skeletal muscle

Answer 13

• action potential in muscle membrane
• depolarisation of T tubules
• open sarcoplasmic reticulum Ca2+ release channels
• increases intracellular ca2+ conc.
• Ca2+ binds to troponin c
• tropomyosin moves and allows interaction of actin and myosin
• cross-bridge cycling and force-generation
• Ca2+ re-accumulated by sarcoplasmic reticulum = relaxation

Question 14

What is smooth muscle?

Answer 14

• Multi-unit smooth muscle
• each fibre behaves as a separate unit
• dense innervation

Unitary (single unit) smooth muscle

• cells are linked by gap junctions
• characterised by spontaneous pacemaker activity

Question 15

where can you find smooth muscle?

Answer 15

• its important in maintaining homeostasis and is found in the walls of
• blood vessels
• gastrointestinal tract and gallbladder
• ureter and urinary bladder
• uterus
• respiratory system
• eye

Question 16

What are smooth muscle cells?

Answer 16

• -a single nucleus with a diameter of about 5micrometer and a length from 20 to 500 micrometer
• each cell is surrounded by a basal lamina and there is a small amount of connective tissue between cells - allows for passage of nerve tracts and blood vessels

Question 17

there are different types of contractions in smooth muscle depending on its location. provide some examples

Answer 17

• oesophagus =phasic, contracting only when food enters
• intestine= phasic contraction and relaxation to push contents along the gut
• sphincters = tonic contractions which only relax to allow material to pass through
• vascular smooth muscle = tonic contraction can control the pressure and quantity of the blood in a particular tissue

Question 18

how is smooth muscle different to skeletal?

Answer 18

• contractile unit is similar, but without regularity
• capable of greater degree of contraction than skeletal muscle
• slow onset and relaxation
• prolonged contraction
• cross-bridge cycling slower

Question 19

how does smooth muscle contract?

Answer 19

• Ca2+ enters the cell and induces release of Ca2+ from the sarcoplasmic reticulum. Ca2+ binds to the calmodulin (CaM). Calmodulin activates myosin light chain kinase (MLCK) resulting in phosphorylation which leads to the activation of the myosin head to attach to actin. In the presence of ATP the myosin head bends producing contraction.

Question 20

how does relaxation occur in smooth muscle?

Answer 20

A calcium pump is required to bring about relaxation

• pump acts on as lower timescale from that in skeletal muscle
• myosin phosphatase important in cessation of contraction
• time to relaxation determined by myosin phosphatase levels

Question 21

What is the arrangement of cardiac muscle?

Answer 21

• the spiral arrangement of the muscles results in the upward squeezing of the ventricular blood from the apex during ventricular contraction
• the intercalated discs contain desmosomes which transfer the force from cell to cell and gap junction that allow for the passage of electrical signals

Question 22

What is the structure of cardiac muscle cells?

Answer 22

• they are relatively small (10-20micrometers in diameter and 50-100micrometers)
• a cardiac cell has a single centrally placed nucleus
• the t tubules are short and broad (larger than skeletal) and no triads
• the sarcoplasmic reticulum is not in the form of an expanded cisterna but organised as an anastomosing network
• cardiac muscle is almost completely dependent on aerobic metabolism and so cells contain a lot of mitochondria. There are glycogen and lipid inclusions which are stores of energy and the myoglobin store oxygen
• each cardiac cell contact several others via intercalated discs

Question 23

How do intercalated discs within the cardiac muscle work?

Answer 23

• they are formed from plasma membrane of 2 adjacent cells which are exclusively intertwined and bound together by gap junctions and desmosomes. the binding together of the cells mechanically, chemically and electrically results in their acting together. The sarcomeres of cardiac muscle have the same banding pattern as skeletal muscle but unlike skeletal muscle form branching fibrillar networks continuous in three dimension throughout the cytoplasm.

Question 24

if the cardiac muscle doesn’t contract with neural stimulation, how does it contract?

Answer 24

• the pacemaker are specialised cardiac muscle cells which are more excitable than the others and therefore contract first. Innervation of these cells by the nervous system can adjust the rate at which they contract.

Question 25

how is an action potential generated in cardiac muscle?

Answer 25

in cardiac muscle the action potential originates spontaneously int he pacemaker cells and spreads through the gap junctions in the intercalated disks to the contractile cells. Desmosomes in the intercalated disks link the adjacent cells forming a physical bond that resists mechanical stress and therefore resists stretching as the heart fills with blood and increases in tension as the muscle fibres contract

Question 26

how does contraction and relaxation occur in the cardiac muscle?

Answer 26

• the action potential enters from an adjacent cell opening the calcium gated voltage channels and Ca2+ enters the cell which induces local release of calcium. the Ca2+ binds to troponin to initiate contraction.
  Relaxation occurs when the Ca2= unbinds from troponin and the Ca2+ is pumped back into the sarcoplasmic reticulum to be stored ready for the next contraction.