Membrane physiology

Question 1

Describe the two types of diffusion and the factors that determine the rate of diffusion

Answer 1

1. Simple diffusion:
   
   • Movement through lipid bilayer if lipid soluble​​
   • Movement through water channels if lipid insoluble
   • rate is determined by:
     
     • Amount of substance available
     • velocity of kinetic motion
     • number and size of openings in a membrane through which the molecules can move
2. Facilitated diffusion
   
   • Requires a carrier protein
   • Requires a chemical binding process to move the molecules
   • May or may not move molecules against a concentration gradient
   • Requires additional energy over and above kinetic energy

Question 2

Describe how the protein channels can selectively allow passage of water and other substances

Answer 2

• Size of the channel pore
  
  • eg. aquaporin have a narrow channel that allows water molecules to pass in single file
• The density of the channel proteins can alter the rate of diffusion
• Channels can be selectively permeable allowing passage of only certain substances
• Channels can be regulated by “gates”
  
  • voltage-gated channels will open with a certain electrical charge
  • Ligand-gated channels open with specific chemical binding

Question 3

Briefly describe facilitated diffusion.

Answer 3

• Facilitated diffusion requires a transmembrane carrier protein.
• A substance can enter the protein that must bind to a specific binding site.
• Binding to the binding site causes a conformational change in the carrier protein
• The conformational change opens the opposide side.
• Diffusion then occurs based on the diffusion gradient
• Molecules can move either way through many carrier proteins

Question 4

Note two of the most important examples of facilitated diffusion within the body

Answer 4

1. Glucose
   
   • Via the family of GLUT proteins
   • GLUT-4 is activated (ligand-gated) by insulin
   • Facilitated diffusion of glucose through GLUT-4 can increase 10- to 20-fold in insulin sensitive tissues
2. Amino acids

Question 5

What is active transport?

Provide an example

Answer 5

• Active transport is the active movement of ions or substances across a cell membrane against a diffusion gradient.
• The process of active transport requires cellular energy
• Sodium and potassium are moved out of and into the cell respectively to help maintain a high intracellular potassium concentration and low intracellualr sodium concentration.
• Calcium, hydrogen, iron, chloride, urate, sugars and most amino acids are also transported actively

Question 6

Briefly note the action of the sodium potassium pump

Answer 6

• 3 sodium and 2 potassium ion binding sites exist on the interior and exterior of the pump respectively
• When 3Na+ and 2K+ ions are bound, the ATPase function is activated and ATP is cleaved to ADP, releasing energy
• This energy release causes a conformational change are helps move the sodium out of the cell and the potassium inwards

Question 7

Describe the vital roles of the sodium and potassium pump with regards to cell homeostastis and function

Answer 7

• Ensures low sodium and high potassium within the intracellular fluid
• Largely responsible for the total cell volume as water movement is linked strongly to sodium movement (via osmosis)
  
  • Activity of the pump is increased if there is evidence of cellular swelling
• Ensures maintenance of an electrochemical gradient - negative within the intracellular space

Question 8

Describe the pumps responsible for maintaining intracellular cytosolic calcium at ~ 10,000 time less than the extracellular fluid

Answer 8

• Transmembrane calcium pump
  
  • Pumps cytosolic calcium out of the cell
• Intracellular calcium pump
  
  • Pump calcium actively into intracytoplasmic vesicles within the sarcoplasmic reticulum or mitochondria
• Both pumps have the same characteristics
• The pump has specific binding sites for calcium and utilises ATPase for energy generation

Question 9

Briefly describe co-transport

Give an example of a co-transport mechanism

Answer 9

• The concentration gradient of a molecule, primarily achieved via active transport provides a store of energy
• The highly concentrated substance can move passively or via a carrier protein in the cell membrane
• For certain carrier proteins, the highly concentrated substance together with a another “passenger” molecule must bind to activate the protein
• The concentration gradient draws the substance along via simple diffusion while the passenger substance is pulled along

Sodium-glucose cotransport - glucose is moved into the cell together with a single sodium ion.

Question 10

Describe the process of transport across cellular sheets.

Where is this process most important

Answer 10

• Substances are generally absorbed via passive of facilitated diffusion at one side - often the luminal surface
• Active transport occurs at the basal and lateral membranes
• Active transport of sodium at the baso-lateral membranes also allows for osmosis of water - due to increased sodium concentration
• Active transport helps to maintain the concentration gradient for diffusion at the luminal surface

This process occurs primarily within the GIT epithelium, gallbladder epithelium and within the renal tubular epithelium

Question 11

What is the resting membrane potential?

How does the resting membrane potential originate?

Answer 11

• The resting membrane potential is the electrochemical gradient determined by the differential concentration gradients of charged particles across a membrane together with the permeability of the membrane to each of the ions
• The sodium and potassium ratios between the intra- and extra-cellular fluid is as follows:
  
  • Potassium = 35 (140 mEq inside / 4 mEq outside)
  • Sodium = 0.1 (142 mEq outside / 14 mEq inside)
• Potassium contribution to membrane potential is -94 mV
• Sodium contribution to membrane potential is +61 mV
  
  • combined and based on the relative diffusion potential of potassium (100 x sodium), the overall membrane potential is -86 mV
• Sodium potassium pump adds about -4 mV due to continual removal of +ve charge from the cell in Na+.
• Note: The membrane potential of the various cell types varies immensely

Question 12

What is an action potential?

Answer 12

• An AP is a rapid change in membrane potential from negative to positive and an almost as rapid repolarisation back to negative. This change in membrane potential is transitory and propogating along a nerve cell fibre

Question 13

Describe the three stages of the action potential

Answer 13

1. Resting stage:
   
   • The nerve fibre is said to be “polarized” during this phase.
   • The resting nerve cell membrane potential is approximately -70 mV
2. Depolarisation stage:
   
   • The membrane becomes suddenly permeable to sodium ions
   • Sodium ions rush into the cell
   • In large axons, large sodium inflows causes an overshoot to positive membrane potential
   • In smaller nerve cells the membrane potential approaches zero
3. Repolarisation stage:
   
   • The sodium channels rapidly close
   • Potassium channels open to a greater degree than normal
     
     • Potassium rushes to the outside of the cell re-establishing the resting membrane potential

Question 14

Describe the 4 channels that are involved in the ion flows during propogation of an action potential

Answer 14

1. Voltage-gated sodium channel
   
   • activated as the resting membrane potential becomes less negative (ie. more positve)
   • Activated around -55 mV
   • Allows a rapid increase in sodium transport into the cell
   • The same voltage change that opens the activation gate also closes the inactivation gate. The inactivation gate closes more slowly than the activation gate
   • Inactivation gate usually remains closed until the resting membrane potential has again been reached
2. Voltage-gated potassium channel
   
   • Open as the membrane potential becomes less negative
   • Slower to open than the sodium channels - open around the same time that the sodium channels are inactivated
   • Potassium outflow helps to restore the negative resting membrane potential
3. NaK ATPase pump
   
   • Primarily for maintenance of the resting membrane potenital
4. K+ Leak channel

Question 15

Briefly describe the role of calcium in the generation / propogation of the action potential

Answer 15

• Calcium pump and voltage-gated calcium channels help maintain very low calcium concentration within the cytosol
• The calcium concentration is ~ 10,000-fold greater in the extra-cellular fluid
  
  • This creates a marked diffusion gradient and electrochemical driving force
• The voltage-gated calcium channels open in response to an increasing membrane potential (or depolarisation)
  
  • They open 10-20 times slower than the sodium channels
• As they are slow to open, they provide a more sustained depolarization, whereas the sodium channels play a key role in initiating action potential

Question 16

Describe the changes that lead to increased excitability of cell membranes when there is a calcium deficit

Answer 16

• A decrease in the interstitial calcium causes sodium channels to become more sensitive
  
  • Sodium channels will open when there is only a small increase in the resting membrane potential
  • Less calcium binding to the sodium channels likely affects the change in voltage required to open the gate
• The increased sensitivity can eventually cause sodium channels to open spontaneously causing random AP generation
• This increased excitability in peripheral motor nerves can lead to twitching and tetany

Question 17

Briefly describe the ionic changes that trigger generation of an action potential

Answer 17

• The AP is triggered when there is an increase in the resting membrane potential
• The sodium inflow through the sodium channels needs to exceed the potassium lost via the slow potassium channels and overcome the changes due to the NaK pump.
• As the sodium inflow exceeds the potassium outflow, the membrane potential increases. This leads to the positive feedback mechanism and initiation of an AP
• An increase of 15-30 mV will trigger an AP

Question 18

Describe how a single action potential can propogate along the entire length of the axon / cell membrane

Answer 18

• The intial action potential involves a rapid inflow of sodium ions, increasing the local membrane potential.
• The local increase is not isolated and will increase the adjacent membrane for 1-2 mm above threshold
• The adjacent membrane crosses threshold and more sodium channels open
• The sodium channels and thus the AP open rapidly along the entrie length of the cell membrane - axon in nerve cells

Question 19

What is myelin and how is it produced

Answer 19

• Myelin is produced by Schwann cells
• Schwann cells envelop a nerve cell axon and rotate around it multiple times
• During this process they lay down multiple layers of Schwann cell membrane
  
  • The membrane contains the lipid substance sphingomyelin

Question 20

How does myelin affect and influence nerve cell AP transmission

Answer 20

• Myelin is an excellent electrical insulator
  
  • Reduces ion flow through the membrane by 5000-fold
• Small gaps are left in the myelin sheath adjacent each site of each Schwann cell
  
  • These gaps are called the node of Ranvier
• The electrical current is transferred between the nodes through both the intra- and extra-cellular fluid
  
  • This is referred to as saltatory conduction

Question 21

Discuss the benefits of conduction along myelinated nerves

Answer 21

• Depolarisation jumps from node to node
  
  • AP conduction velocity can be increased 5- to 50-fold
• There is much less ionic transfer across the cell membrane
  
  • Much less energy is required to restore the ionic gradient across the cell membrane
    
    • Energy to restore the ionic gradient is primarily used by the NaK ATPase pump
• As there is much reduced ionic transfer across the cell membrane, repolarisation can occur with little ionic transfer

Question 22

What are the major triggers that lead to generation of an action potential.

Provide an example of each

Answer 22

Any trigger that causes sodium ion inflow can trigger an AP

• Mechanical disturbance
  
  • Pressure sensation in the nerve endings within the skin
• Chemical effect
  
  • Neurotransmitters within the brain
• Passage of electrical impulse
  
  • Passage between adjacent or successive muscle cells in the heart or intestine

Question 23

Describe the general mechanism of muscle contraction

Answer 23

1. AP travels along a motor nerve terminating at a muscle fibre
2. The nerve ending secretes a small amount of ACh
3. ACh acts locally on the muscle cell membrane to open ACh-gated channels
4. ACh-gated channels open allowing sodium inflow into the cell. This causes local depolarisation and opening of fast sodium channels - AP initiated on the muscle cell membrane
5. AP travels along the muscle cell membrane
6. The energy from the AP causes the release of calcium ions from the sarcoplasmic reticulum (via voltage-gated channels)
7. Calcium ions initiate attractive forces between the actin and myosin filaments causing them to slide alongside each other
8. After a fraction of a second the calcium ions are pumped back into the sarcoplasmic reticulum via a Ca²⁺ pump
9. Calcium removal causes the muscle cell contraction to stop.

Question 24

Describe the three sources of enegy that are utilised for muscle contraction.

Note that the energy is provided in the form of ATP

Answer 24

• Energy is utilised by the myosin myofilament for the “walk-along” mechanism than enables muscle contraction
• Energy is also utilised to restore calcium concentrations (calcium pumps) and both sodium and potassium concentrations.

1. Phosphocreatine
   
   • Contains a high energy phosphate bond that is cleaved to convert ADP to ATP
2. Glycolysis
   
   • anaerobic process that involves the breakdown of glycogen into glucose and subsequently into pyruvate and lactic acid.
   • Liberates energy that converts ADP to ATP and helps restore phosphocreatine levels
   • ATP regeneration is ~2.5 x faster than from aerobic metabolism
3. Oxidative metabolism
   
   • Involves the combining of oxygen with the end products of glycolysis and other food stuffs in the cells to form ATP
   • Can utilise fatty acids and fats and carbohydrates

Question 25

Describe the characteristics of slow muscle fibres

Answer 25

• Smaller than large fibes
• Innervated by smaller neurons
• More extensive blood vessel network for provision of oxygen
• Increased mitochondria when compared to large fibres
• Large volumes of myoglobin
  
  • Myoglobin binds oxygen to store it for use on demand

Question 26

Describe the characteristics of fast muscle fibres

Answer 26

• Large than slow fibres for increased force of contraction
• Extensive sarcoplasmic reticulum for calcium storage
  
  • Provides a sotre for rapid calcium release during contraction
• Large amount of glycolytic enzymes
• Less extensive vascular supply
• Fewer mitochondria when compared to slow fibres
• Less myoglobin than slow fibres

Question 27

Describe the important neurological aspects of the maintenance of normal skeletal muscle tone

Answer 27

• Even at rest, there is a degree of muscle taughtness or tone
• As muscle contraction of any sort requires an action potential, muscle tone is initiated by a low rate of small nerve impulses coming from the spinal cord
• The spinal nerve impulses are in part controlled by the CNS and partly controlled by the signals that originate in the muscle spindles

Question 28

Briefly describe the cellular process that lead to muscle fatigue

Answer 28

• Fatigue results from the inability of the contractile elements and the underlying metabolic processes to continue to supply an appropriate work output
• The degree of fatigue increases in almost direct proportion to depletion of glycogen stores within the muscles
• Prolonged intense activity can also lead to mild diminishing of nerve output and reduced AP generation
• Interruption of blood flow and thus oxygen through a contracting muscle will lead to fatigue rapidly (within 1-2 minutes)

Question 29

Describe the major components of the neuromuscular junction

Answer 29

• Terminal portion of a large myelinated nerve fibre
  
  • Branches to supply 3-100’s of individual muscle fibres
  • Contains large numbers of mitochondria to synthesis ATP - the energy source for ACh synthesis
  • Contains vast numbers of synaptic vesicles containing acetylcholine
• The nerve ending sits within a synaptic trough of the corresponding muscle cell
  
  • There are numerous invaginations or folds of the muscle cell membrane to greatly increase surface area
    
    • These folds are called subneural clefts
• The synaptic cleft/space is ~20-30 nm wide
• Acetylcholine esterase is present in large quantities in the synaptic cleft

Question 30

Describe the process by which acetylcholine is released from a pre-synaptic nerve terminal

Answer 30

• AP spreads down the nerve to the terminal
• AP stimulates the opening of voltage gated calcium channels
• Calcium diffuses into the axon cytoplasm
• A calcium dpendent protein cascade occurs
  
  • Vesicles are released from the cytoskeleton
  • Vesicles move to the active zone adjacent the nerve terminal
  • Eventually, the ACh vesicles anchor to the pre-synaptic cell membrane
• Docking of the vesicles leads to fusion of the vesicular membrane with the cell membrane and release of ACH into the synaptic cleft

Question 31

Briefly describe the interaction between acetylcholine and the acetylcholine receptor together with the down stream effects

Answer 31

• ACh is released into the synaptic cleft after nerve stimulation by an action potential
• The ACh diffuses across the synaptic space with 2 ACh molecules required to bind to the ACh receptor for activation
  
  • The ACh receptor is composed of 5 protein subunits that essentially form a tube.
  • Binding of ACh to the two alpha subunits causes a conformational change
• Sodium ions are allowed to passage the ACh receptor once it has been activated
• Sodium entry into the cell increases the membrane potential and activates fast sodium channels
• This ensure propogation of the AP along the muscle cell membrane

Question 32

Describe the various drugs or processes that can alter the function of the neuromuscular junction

Answer 32

1. Stimulants
   
   • Nicotine, carbachol, metacholine can all act on the AChR similarly to ACh itself
   • These substances are often not broken down by ACh esterase
   • Can have a prolonged activity causes repeated muscle stimulation / AP generation
2. Stimulants that act by inactivation of AChE
   
   • Neostigmine, physostigmine, pyridostigmine
   • Most of the drugs bind and inactivate AChE for several hours
   • Diisopropyl fluorophosphate - nerve gas agent - dines to AChE for several weeks
3. Blocking agents
   
   • Curariform drugs
     
     • Block the action of ACh on the receptor
   • Botulinum toxin
     
     • Blocks the release of ACh from the presynaptic nerve terminal
4. Immune disease
   
   • Myasthenia gravis
     
     • Antibodies attach to an inactivate / destroy the acetylcholine receptor on the post-synaptic membrane

Question 33

Describe the movement of calcium ions into and out of the sacoplasmic reticulum during muscle contraction

Answer 33

• Calcium ions are stored in abundance within vesicles in the sarcoplasmic reticulum
• ACh binding to the AChR allows Na+ inflow - this opens Na+ channels and initiates an AP in the muscle membrane
• The AP propogates along the muscle cell membrane and the T-tubules
• Voltage-gated ryanodine receptor channels activate the calcium release channels in the membrane of the sarcoplasmic reticulum
• Vesicles bind to the SR and release calcium via exocytosis into the sarcoplasm for use in myofibre contraction.
• The sarcoplasmic reticulum Ca²⁺ATPase pump removes calcium from the sarcoplasm - pumps back into the SR
  
  • Additionally, Calsequestrin can bind up to 40 calciumn ions within the SR

Question 34

Briefly describe the suspected pathophysiology of malignant hyperthermia

Answer 34

• Genetic mutations in the ryanodine receptor gene have been identified in humans with malignant hyperthermia
  
  • Similar defects have been noted in dogs, however malignant hyperthermia can occur despite the presence of a normal ryanodine receptor gene
• MH leads to unregulated passage of calcium ions into the sarcoplasm from the SR.
• Increased calcium within the sarcoplasm leads to uncontrolled muscle fibre contraction
  
  • Sustained skeletal muscle contractions
  • Heat generation due to the large muscle volume in the body
  • Cellular acidosis due to rapid production of lactic acid
• With severe cases, the muscle cells can breakdown and release potassium and muscle cell enzymes (CK being the obvious one) and myoglobin

Question 35

List the classical clinical signs associated with malignant hyperthermia

Answer 35

• Hyperthermia
• Tachycardia
• Tachypnea
• Increased carbon dioxide production
• Increased oxygen consumption
• Acidosis
• Hyperkalaemia
• Muscle rigidity and rhabdomyolysis

All clinical signs are associated with a hyper-metabolic state

Often induced by exposure to the volatile anaesthetic agents or with excessive exercise in some dog breeds

Question 36

Describe the treatment recommendations for malignant hyperthermia

Answer 36

• Active cooling
• Fluid support
  
  • Cooled fluids
  • Close monitoring of serum potassium levels
  • Increase GFR to manage pigmenturia and potential renal damage
• Dantrolene
  
  • Antagonises the ryanodine receptors
  • Inhibits release of calcium from the sarcoplasmic reticulum and can blunt the underlying process

Question 37

Note the major anatomical similarities and differences between smooth and skeletal muscle

Answer 37

• Smooth muscle are tiny in comparison with skeletal muscle fibes up to 30 times as wide and hundreds of times longer
• Smooth muscle does not contain the troponin complex that is necessary for control of skeletal muscle contraction
• Both utilise sliding actin and myosin myofibrils
  
  • Both sets of myofibres respond and contract in response to calcium release from the SR
  • Both sets of muscle cells are essentially innervated by a single neuron

Question 38

Describe the 5 ways in which the various types of smooth muscle are distinctive

Answer 38

1. Physical dimensions
2. Organisation into bundles or sheets
3. Response to different types of stimuli
4. Characteristics of innervation
5. Function

Question 39

What are the characteristics of multi-unit smooth muscle?

Answer 39

• Each fibre operates independently and is often innervated by a single nerve ending
• Outer layer is covered with a glycoprotein and fine collagen mixture that helps insulate each fibre from those adjacent
• Each fibre can contract independently
• Controlled by nerve signals

Examples:

• Ciliary muscle of the eye
• Iris muscle of the eye
• Piloerector muscles that cause erection of the hairs

Question 40

What are the major characteristics of unitary smooth muscle

Provide examples of unitary smooth muscle

Answer 40

• Also called syncytial muscle or visceral smooth muscle
• Masses of hundreds of muscle fibres contract together as a single unit
• Arranged in sheets or bundles
• Cell membranes are adherent to adjacent cells
  
  • Contractile force can be transmitted to the adjacent cell
• Cells are joined by gap junctions
  
  • ​Ions can travel freely between cells triggering contraction without an AP
  • AP can travel between cells also
• All above leads to synchronized contraction

Examples:

Visceral organs - gastrointestinal tract, urinary tract, bile ducts

Many blood vessels

Question 41

Describe the structures of smooth muscle as they relate to contractile ability

Answer 41

• Multiple dense bodies througout the cell
  
  • Some are attached to the cell membrane
  • Intercellular bonding proteins link dense bodies from adjacent cells
• Large numbers of actin filaments extend from the dense bodies
• A single myosin filament lies centrally between two dense bodies
• The myosin filament has side-polar cross bridges
  
  • The opposite sides hinge in the opposite direction
  • The smooth muscle cell can contract as much as 80% of their length (30% for skeletal muscle)

Question 42

Describe the contrasting characteristics of smooth versus skeletal muscle contraction at a cellular level

Answer 42

• Myosin cross bridge cycling in smooth muscle is slow, skeletal muscle is rapid
• Less ATPase activity in the myosin head likely contributes due to slower ATP degradation
  
  • ATP cycling fuels the attachment and release of the myosin cross bridges and head movement
• Low energy utilisation during smooth muscle contraction primarily due to reduced ATP cycling
• Smooth muscle is slow to start contracting and contraction lasts much longer ~ 30 times as long
• Increased force of contraction in smooth muscle due to prolonged attachment of the myosin cross-bridge
• “Latch mechanism” allows for prolonged maximal smooth muscle contraction with little energy expenditure
• Stress-relaxation of smooth muscle allows many hollow visceral organs to essentially maintain a stable/steady intra-luminal pressure despite large volume fluctation

Question 43

Describe the role of calcium and calmodulin in smooth muscle contraction

Answer 43

• Calcium is allowed into the cell from the extracellular fluid (and released from the SR) after AP propogation due to activation of voltage gated calcium channels
• Calcium ions bind reversibly with calmodulin
• Calcium-calmodulin activates the myosin light chain kinase
• The myosin light chain becomes phosphorylated
• Once phosphorylated, the myosin head can bind repeatedly with the actin filament and hinge
  
  • This binding occurs in the presence of ATP

Question 44

Describe the way calcium is modulated and altered and the effect on smooth muscle contraction

Answer 44

• Poorly developed sarcoplasmic reticulim
  
  • The majority of calcium originates from the extracellular fluid
  • Trasport of extracellular calcium is slow when compared to release from the SR
• Force of contraction of smooth muscle is highly dependent on the extracellular calcium concentration
  
  • This is not the case for skeletal muscle due to large calcium storage within the SR
• An ATP dependent calcium pump removes excess calcium
  
  • This pump is much slower than the SR calcium pump
  • Prolonged and slow contraction
• Myosin phosphatase is required to split the phospahte from the myosin regulatory light chain
  
  • This process stops the cycling process and terminates contraction

Question 45

Describe the various stimuli that elicit an AP in smooth muscle

Answer 45

• Electrical impulse - from neurons
• Chemical message
  
  • Hormones
• Stretch receptors
• Spontaneous generation within the fibre itself

Question 46

Describe how and why smooth muscle can produce an action potential with a plateau

Answer 46

• The plateau phase of the smooth muscle action potential allows for a prolonged force of contraction
  
  • Useful in the uterus, ureter and within certain types of vascular smooth muscle
• Smooth muscle has few voltage-gated sodium channels
• Calcium flow to the interior of the cell is responsible for the propogation of the smooth muscle AP
• Calcium channels open far slower than sodium channels
• Calcium channels remain open for a prolonged period of time
• Calcium acts to propogate the AP and also work on contractile elecments

Question 47

Describe the slow wave potential present in numerous smooth muscles

Why is the slow wave potential important?

Answer 47

• The slow wave potential is a local property of the smooth muscle cell membrane
• There is a rhythmic change in the membrane potential
• Specific cause for the slow wave is unknown
  
  • Changes in ion transport outward through the membrane (likely Na⁺ pumping)
  • Rhythmic change in conductance of the ion channels
• When they are “strong” enough they can elicit an AP and therefore smooth muscle contraction
• This “pacemaker” potential is important for the rhythmic contractions of the gut

Question 48

Describe the various local control signals for smooth muscle contraction, giving examples.

Answer 48

• The smooth muscle of arterioles, meta-arterioles and pre-capilliary sphincters have little to no nervous supply
• In the normal resting state, these vessels remain contracted to preserve blood pressure
• These vessels can relax in certain circumstances to allow increased blood flow:
  
  • lack of local tissue oxygen concentration
  • Excessive carbon dioxide
  • Increased hydrogen ion concentration
  • Adenosine
  • Lactic acid
  • Increase potassium
  • Nitric oxide
  • Increased body temperature

Question 49

List the various hormones that can have an effect of smooth muscle tone

Answer 49

• Epinephrine
• Norepinephrine
• Angiotensin
• Endothelin
• Vasopressin (ADH)
• Histamine
• Oxytocin
• Serotonin

Question 50

Describe the mechanisms by which the excitability of smooth muscle can be increased or decreased by the effect of hormones.

Answer 50

• Various hormones bind to receptors that will then directly impact the state of either sodium or calcium channels

​Excitation

• The net result can be depolarisation, generation of an AP or enhancement of already present APs
• Hormone may stimulate internal changes within the cell that trigger release of calcium from SR - contraction without an AP

Inhibition

• Hormone may initiate closure of the sodium or calcium channel
• May increase opening of the potassium channels - increase potassium leak decreases the membrane potential
  
  • Can trigger hyperpolarisation which strongly inhibits muscle contraction
• May activate production of intracellular cAMP or cGMP (messenger proteins)
  
  • These can alter the phosphorylation of various enzymes thereby altering contraction
    
    • Increased activity of the calcium pumps on both the SR and cell membrane –> reduce cytosol calcium and therby contaction

Question 51

Briefly describe the actions and interactions of the two major smooth muscle neurotransmitters

Answer 51

1. Acetylcholine
2. Noradrenaline

• Both are secreted by neurons but not the same neuron
• Both neurotransmitters can trigger either excitation or inhibition depending on the receptor types on the surface of the smooth muscle
• When acetylchoine is excitatory, noradrenaline is typically inhibitory, and vise versa
• The interplay between these two neurotransmitters is essential for normal function of the autonomic nervous system and maintenance of appropriate smooth muscle tone