Cell Signalling and Membrane Potential*

Question 1

Signal transduction?

Answer 1

Method by which information is transmitted from outside the cell tot inside the cell and then translated into a physiological response

Question 2

Ligand/agonist? (competitive vs non-competitive?)

Answer 2

Substance which binds to a receptor

Question 3

Receptor?

Answer 3

Protein found on/in a cell which selectively binds a particular ligand and transmit the signal onwards to the effector

Question 4

Effector?

Answer 4

Element that responds to activation of the receptor and is responsible for the initiation of the cellular response

Question 5

Types of receptors?

Answer 5

Ion channels
GPCRs
Tyrosine kinase receptors
Intracellular receptors

Question 6

Specificity?

Answer 6

Interaction between ligand and receptor is specific

Question 7

Sensitivity?

Answer 7

High affinity between ligand and receptor

Question 8

Cooperativity?

Answer 8

Small change in ligand conc produces large change in response

Question 9

Ion channels - function? Vm? dental application?

Answer 9

Redistribute charge, change membrane potential and stimulate/inhibit cell
Vm more negative cell harder to stimulate and vice versa
LA - block Na chs
Benzodiazepine - indirectly block GABAa receptor and alter (increases) GABA affinity to receptor

Question 10

Local anesthetic- basic structure? characteristics? combo? Fibre sensitivity?

Answer 10

Ester or amine bond
Lipid sol of aromatic region determines membrane crossing ability
Amine side blocks Na ch
LA combined with ADR to cause vasoconstriction
LA needs to be ionised LAH+, reduced efficiency in acidic areas (infection, reduces membrane crossing)
Pain, postgang, pregang and temp

Question 11

Benzodiazepine sedatives - how it works?

Answer 11

Midazolam
Act on GABAa
Bind increases affin of GABA binding, increasing opening freq and so increased Cl- causing CNS suppression
Barbiturates also act on GABAa but increase duration causing anesthesia

Question 12

Second messenger - definition and function? examples and their effectors?

Answer 12

Sol products of mem bround enzymatic reactions which are released into the cytoplasm to elicit a physiological effect
Transfer signal from membrane to rest of cell
AC - cAMP
Phospho C - IP3 and DAG
Phospho A2 - arachidonic acid

Question 13

Adenylate cyclase linked receptors - variations? stim and inhib receptors?

Answer 13

Gi and Gs
Stim - B-adr, ACTH and gonadotropins
Inhib - A2, musc, opiate and GABAb

Question 14

cAMP action - B2 (action)? B1 (action)? prostacyclin (action)? M2AChR (action)? A2 (action)? and opiod/GABAb (action)?

Answer 14

Act PKa
B2 - increases glycogen meta in liver, fat and muscle
B1 - increases Ca ch activity in the heart
Prostacyclin - phospho MLCK, which impedes SM contraction (bronco/vasodilation)
M2 AChR - decreases HR
A2 - inhibit NuT, insulin and contract SM
Opioid/GABAb - open K+ causing hyperpol and inhibits volt gated Ca causing CNS depression

Question 15

Opioid analgesics - example? natural? receptors?

Answer 15

Morphine and codeine
Endorphins/enkephalins
Receptors such as gamma, kappa and delta, gamma receptor for analgesic effect with most side effects

Question 16

Phospholipase C system - effector? regulator? 2nd messenger? IP3 effects and PKc effects?

Answer 16

Phospho C
PLC reg by Gq
IP3 and DAG
IP3 increases intracell Ca
DAG activates PKc
IP3 + DAG --> PIP2
IP3 increases musc contract, hormone and NuT release, cardiac contraction force and cell death
PKc increases SM contract, tumour promotion, stim ion transport, release NuT, inflamm response and receptor desense

Question 17

Phospholipase A2 - process? further meta? metabolite action?

Answer 17

Membrane phospholipids broken down by phospholipase A2 to form arachidonic acid
Into prostaglandins, prostacyclin and thromboxane
Cause inflamm response, hyperalgesia and tumor production

Question 18

Receptor Tyrosine kinase - main actions? signalling process?

Answer 18

Stimulate growth or arrest growth and promote differentiation
Pathway becomes unregulated in cancer
Grb2 bind to Pi
Act Ras, act Raf, act Mek, act MAPK act transcription factors

Question 19

Intracellular receptors - location? binding causes? dimer binds to? steroid hormone (gene switching off)? characteristic?

Answer 19

Exist in the cytoplasm
Causes dimerisation
Binds to a HRE
Steroid hormones - potent anti-inflamm agents by switching off COX, iNOS, IL-1/6 and TNFa
Steroid, thyroid, retinoic and vit D
Slow onset but persistent appearance

Question 20

The NMJ - consists of? motor end plate receptors? signal transduction and breakdown? nicotinic cholinergic receptor opening?

Answer 20

Consists of axon terminals, motor end plates on the muscle membrane and Schwann cell sheaths
Motor end plate contains a high conc of ACH receptors
AP travels to the synaptic knob, this causes the volt-gated Ca chs to open allowing Ca into the presynaptic membrane
Ca binds to the docking protein allowing the ACh vesicles to bind the membrane (via exocytosis), and is released into the cleft onto the nicotinic ACh receptor
The ACh is broken down by AChe to form acetyl + choline
NCR binds 2 ACh molecules, this allows Na to enter and K to leave

Question 21

7 classes of NuT and examples?

Answer 21

ACh
Amines:
- tyrosine forms dopamine, noradrenaline and adrenaline
- tryptophan forms serotonin (prozac inhibits 5-HT uptake)
- histadines forms histamine
Aas
- glutamate (excitatory CNS)
- aspartate (excitatory brain)
- GABA (inhibitory brain)
- glycine (inhibitory SC)
Purines
- AMP and ATP
Gases: formed on demand
- NO and CO (retrograde signalling)
Peptides: large dense vesicles
- substance P and opioid peptides
Lipids: formed on demand
- eicosanoids (intracellular sig)
- cannabinoids (intracellular signalling)

Question 22

Types of receptors - cholinergic, adrenergic and glutamate? (linkage, ions and variations?)

Answer 22

Cholinergic: CNS/PNS ACh
- nicotinic; monovalent cation channels (Na and K)
- muscarinic; linked to gprots (GPCRs)
Adrenergic: CNS/PNS NA and ADR
- alpha (nerve terminals) and beta (muscles)
- linked to gprots (GPCR)
Glutamate: CNS
- AMPA, kainate and NMDA; mono or divalent cation ch (Na, K and Ca for NMDA)
- metabotropic Glu receptors (mGluRs) (linked to gprots)

Question 23

Neurotransmitter inactivation - types/examples? ACh synthesis and recycling?

Answer 23

Axon terminals or Glial cells
NuT can diffuse out of the cleft
ACh synthesis and recycling:
- ACh formed from choline and acetyl CoA with help from an enzyme
- ACh is broken down by AChe in the synaptic cleft into choline and acetate
- Choline is transported back into the axon terminal and reused to make more ACh

Question 24

Electrical and concentration gradients of a typical cell?

Answer 24

Na in - 15mM
Na out - 145mM
K in - 140mM
K out - 5mM
Cl in - 30mM
Cl out - 110mM
Ca in - 0.0001mM
Ca out - 2mM

Question 25

Spatial summation - definition? presynaptic axon terminals? graded potentials?
Temporal summation - definition?

Answer 25

Spatial summation: space
- dependent on the presynaptic axon terminals if they are excitatory or inhibitory
- graded potentials arrive at trigger zone together and sum to create a threshold signal forming a AP
- if one of the presynaptic axon terminals is inhibitory, the summed potentials are below the threshold and sp no AP
Temporal summation: time
- 2 graded potentials will not cause an AP if they are far apart in time
- 2 graded potentials will cause an AP if they are close together (reach threshold)

Question 26

Presynaptic inhibition - process? Postsynaptic inhibition - process?

Answer 26

An inhibitory neuron can reach the presynaptic axon terminal and inhibit the release of the NuT and so no response can occur
Postsynaptically, several neurons can arrive at a dendrite and the summed response (EPSP and IPSP) will decide the response of the postsynaptic neuron

Question 27

Convergence and divergence integration - definition?

Answer 27

Divergent: one presynaptic neuron goes to affect several postsynaptic neurons
Convergent: many presynaptic neurons converge and influence a postsynaptic neuron

Question 28

Function of anaesthetics/analgesics? muscle relaxants? drug therapies?

Answer 28

Anaesthetics:
- disrupt AP propagation (lignocaine) and synaptic transmission (barbiturates)
Muscle relaxants:
- block NMJ (tubocurarine non-depol and succinylcholine depol)
Drug therapies:
- enhance transmission (antiAChe) and BoTox

Question 29

Glutamatergic receptor - signal transduction?

Answer 29

Glutamate released
Na entry via AMPA-R depol postsynaptic cell
Mg eject and NMDA-R channel opens
Cell sensitised to glutamate
Paracrine enhances glutamate release

Question 30

What factors allow cells to return to resting membrane potential - BBB? cell ion concentrations?

Answer 30

Electrical and concentration gradient creates a equilibrium
Selective perm of K channels
Na and K in/out
Nernst equation
Blood brain barrier - tight capillaries, due to astrocytes and tight junctions between endothelial cells protecting the brain from K changes
Reaches resting membrane potential from leaky Na channels
Na/K ATPase pump
K+ 140 and 5 (in/out)
Na 15 and 150
Cl 10 and 110

Question 31

Creation of an action potential - what happens to the ion concentrations - Na, Ca, Cl and K? properties of AP?

Answer 31

More K channels and so K flows out and cell hyperpolarises and repolarisation
Open Na channels and so Na flows in and cell depolarises
Open Cl channels and so CL flows in and cell hyperpolarses
Open Ca channels and so Ca flows in and cell depolarises
ALl or none

Question 32

Difference between graded and action potential - staggered firing? self-propagation? stimulus and AP relation?

Answer 32

Graded potential is to decide when an AP is fired
AP is to send an electrical signal over a long distance
Staggered firing due to the refractory period of the Na channels
Self-propagation occurs after the TP is achieved this then opens several voltage-gated Na channels and so are propagated by each other
The greater the stimulus creates a greater # of APs

Question 33

Effect of myelination - formed by? conduction type? myelination effect?

Answer 33

Formed by schwann cells in PNS and oligodendrocytes in the CNS both form the myelin sheath
Both allow saltatory conduction, a fast conduction of the AP
Myelination increases membrane resistance and decreases membrane capacitance (120m/s)

Question 34

Types of nerves and function - sensitivity to LA?

Answer 34

Aalpha - proprioception and motor neurons
Abeta - touch and Pa
Agamma - motoneurons of muscle spindles
Adelta - touch and sharp pain
B - preganglionic autonomic fibres
C - heat and dull pain
C most sensitive to LA

Question 35

Examples of graded potentials - generator? postsynaptic? endplate? pacemaker? properties of GPs? IPSPs and EPSPs/

Answer 35

Generator at sensory receptors
Postsynaptic at synapses
Endplate at NMJ
Pacemaker in SAN/AVN
Decremental - lose of current over distance (only useful for short distances)
Graded - signal stimulus intensity in their amplitude
Depol/hyper - EPSP or IPSP
IPSPs - opening Cl or more K chs and so inhibitory
EPSPs - opening of Na and K, but more Na enters

Question 36

Somatic sensations - definition? differ from other sensory systems? examples?
Touch - receptor type? stimuli? sensory ending examples?

Answer 36

Sensation from the skin, bones, tendons and joints
Receptors are distributed throughout the body and respond to different kinds of stimuli
Examples:
- touch (Meissner’s corpuscle), Pa, temp (free nerve endings), pain (free nerve endings) and proprioception
- Pacinian corpuscle (mechanical distortion)
- muscle spindles (muscle stretch)
Touch:
- mechanoreceptors reside in the dermis of the skin
- sensitive to physical distortion
- monitor contact with the skin
Sensory endings:
- exteroreceptors (skin)
- interoceptors (viscera)
- proprioceptors (muscle and joints)

Question 37

Touch - pathway? function of dorsal column? information provided?

Answer 37

Touch: crosses brain (L for R body)

• dorsal column - medial lemniscal pathway
• dorsal columns carry info about tactile sensation towards the brain
• fine touch, tactile localisation, vibration sense and proprioception

Question 38

Sensation to the face - nerves? touch pathway?

Answer 38

Face:
- trigeminal nerve (V1 upperhead and nose, V2 eye and cheeks and V4 ear and chin)
- C2/C3 at the ramus of mandible
Touch pathway:
- mechanoreceptor from face via either V1/2/3 to the Thalamus (ventral posterior nuc) and then to the primary somatosensory cortex

Question 39

Sensory symptoms - a diagnostic approach and examples?

Answer 39

Pattern of anatomical distribution and mode of onset of numbness, paraesthesia or pain in different situations
Examples:
- migraine (20-30 mins to 1/2 of body)
- vascular lesion (instant)
- sensory epilepsy (sec)
- SC lesion (hours/days to spread)

Question 40

Patterns of sensory disturbance - peripheral nerve lesions? nerve root lesions? SC lesion? brain stem lesions (hemisphere lesion)? (common symptoms)?

Answer 40

PNL:
- sensory loss and simple paraesthesia
- gloves and stocking distribution of sensory loss
NRL:
- pain
- assoc with dermatomal pattern of sensory loss
- C5, C7 and L5
SC lesion:
- brown sequard (unilateral lesion in SC syndrome with sensory loss on same side)
- syringomyelia (central cord lesion with sensory loss id dissociated)
BSL:
- dorsal column sensory system cross midline in upper medulla
- BSL causes sensory loss affecting contralateral side
- HL causes sensation over whole contralateral half of body

Question 41

Sensory deficits in peripheral nerve lesions - ulnar? median? radial? lateral cutaneous? and common peroneal?

Answer 41

Ulnar: palm
- 1.5/5 fingers (except abductor pollicis brevis and ulnar flexors of the little and ring finger and wrist)
Median: palm
- 3.5/5 fingers with the abductor pollicis brevis
Radial nerve: top
- near first 3 digits
- finger extensors, thumb extensors and abductors, wrist flexors and brachioradialis
Lateral cutaneous:
- thigh
Common peroneal:
- lateral foot and lower leg
- toe and foot flexors and foot evertor

Question 42

Dermatomes - definition? upper limb? lower limb? Thorax and abdomen? herpes zoster virus and dermatomes?

Answer 42

Area of skin supplied by a particular spinal/cranial nerve
Upper limb: C5-C8 and T1
- C5/6 lateral
- C8/T1 medial
- C7 central part of hand
- no overlap across axial line
Lower limb: T12-S3
- genitalia S3-S4
Thorax and abdomen:
- T4 at nipple level
- T7 below xiphoid process
- T10 at umbilicus
- L1 at suprapubic region 
Herpes zoster:
- dormant in sensory neurons
- found across a single dermatome

Question 43

Visceral referred pain - definition? examples? heart attack?

Answer 43

Pain felt in one area of the body does not always represent where the problem is because the pain may be referred there from another area
Examples:
- gastric ulcer (epigastric region T7 and T8)
- diaphragm (shoulder C3-C5 and skin over costal margins)
Heart attack:
- pain from the arm
- heart and the arm use the same dermatome/nerve tract but the arm has greater amount of sensory receptors and so the pain is felt greater in the arm

Question 44

Functions of Meissner’s? Merkel’s? Pacinian’s? Ruffini? Free nerve endings? corpuscles

Answer 44

Meissner's - light touch
Merkel's - touch
Pacinian - deep pressure
Ruffini - warmth
Free nerve endings - pain

Question 45

Sensory transduction - types of information received? stronger stimulus? receptive field defintion?

Answer 45

Modality - type of neurons
Intensity
Location of stim
Longer and stronger stimulus - more graded potentials producea more AP in the postsynaptic mem
Receptive field - the size of catchment of sensitivity which determines acuity

Question 46

Transmission of sensory information - mechanoreceptive fibres (dorsal column? synapse? 2nd order fibres? project to?) Thermoreceptive and nociceptive (synapse? 2nd order fibres? project via and to?) Damage to the dorsal column (loss sense)? Damage to anterolateral quadrant (loss sense)? Ultimate termination?

Answer 46

Mechanoreceptive (Aa & Ab fibres):
- project up ipsilateral dorsal columns
- synpase in cuneate and gracile nuceli
- 2nd order fibres cross over midline in brainstem
- project to reticular formation to thalamus to cortex
Thermoreceptive and nociceptive (Ad and C fibres)
- synpase in dorsal horn
- 2nd order fibres cross over midline in SC
- project up through contralateral spinothalamic (anterolateral) to reticular formation to the thalamus to the cortex
Damage to dorsal:
- loss of touch, vibration, proprioception below lesion in ipsilateral side
Damage to anyerolateral quadrant:
- causes loss of nociceptive and temp sense below lesion on contralateral side
Termination:
- somatosensory cortex (S1)

Question 47

Adaptation of neurons (rapid and slow)? Convergence of neurons? Lateral inhibition of neurons? Inhibition of sensory info (higher brain centres?) Perception of sense?

Answer 47

Adaptation:
- rapid: stimulus present but constant, adaption allows reduction in AP firing (Hat in head)
- slow: stimulus present but constant, slow eventually adapt to reduce AP firing
Convergence:
- several stim to one synapse which reduces acuity and underlies referred sensations (specific ascending pathway)
- nonspecific ascending pathway between temp and touch synpase on same synapse reduces acuity
Lateral inhibition:
- activation of one sensory input causes synaptic inhibition of its neighbours
- give better defintion of boundaries
Inhibition of sensory info:
- inhibition from higher brain centres to the sensory neurones
Perception:
- not all information is acted on

Question 48

Segmental control - gate control for pain (Aa/Ab relation with Ad/C fibres)?

Answer 48

Activity in Aa/Ab can inhibit Ad/C fibres as they have a collateral fibre that synapses with the ganglion to inhibit the passage of Ad/C fibres

Question 49

Cell signalling application to the blood vessels?

Answer 49

Regulation of BP
BV contractility
Vascular SM cell length changes

Question 50

Smooth muscle cell anatomy - organelles present?

Answer 50

SR
Myosin
Actin
Elastic components (collagen + elastin)

Question 51

Cross-bridge cycling in SM - calmodulin? MLCK? activated and inactivated myosin? regulation of SM contractility (MLCK?)

Answer 51

Calmodulin:
- Ca binds to calmodulin changing the conformation allowing MLCK to interact
MLCK:
- ATP is used via MLCK to activate the myosin
Contractility:
- contract via MLCK allowing phosphorylation of the chains
- relation via myosin phosphatase to remove Pi

Question 52

Regulation of SM contractility (Ca influence?) reversal of depol induced SM contraction (K+)? regulation of contraction via receptor (agonist example? 2nd messengers? release? activation? action?)

Answer 52

Ca:
- depolarisation opens volt-gated Ca chs
- activates MLCK
- phosphorylates chains
- allowing actin-myosin contraction
Reversal:
- increased Ca opens Ca-act K chs causing repolarisation preventing overstimulation
Receptor:
- endothelin or noradrenaline
- act receptors and phospholipase C that converts PIP2 into IP3
- IP3 activates the release of Ca from stores activates MLCK
- phosphorylates light chain allowing actin-myosin interaction causing contraction

Question 53

Substances which regulate SM contractility (ANS? endothelial-derived factors? myogenic response? blood borne factors?)

Answer 53

ANS: symph
- NAD contraction via a-adrenergic
- ADR relaxation via b-adrenergic
Endothelial:
- NO - relax
- endothelin - contract
Myogenic:
- innate ability of vasc SM to respond to changes in Pa
Blood:
- released by specific organs such as angiotensin II from kidneys

Question 54

NO - produced by? equation? NOS (variations? activators?) ACh eNOS activation process? ADR eNOS activation process?

Answer 54

Produced:
- in endothelial cells
Equation:
- L-arginine + O2 forming NO via nitric oxide synthase (rls)
Variations:
- endothelial eNOS, neural nNOS and inducible iNOS
Activators:
- ACh
- thrombin
- shear stress (activates Akt stimulating eNOS)
ACh:
- act muscarinic receptors
- increases Ca
- Ca binds to calmodulin
- increasing eNOS activity
ADR:
- activates b-adrenergic
- increases cAMP
- activates PKA
- increasing eNOS activity

Question 55

Signal transduction pathway of endothelium vascular relaxation (receptor? Ca? NOS? NO? GC? action?)

Answer 55

Muscarinic receptor activated by ACh increasing Ca, binding to calmodulin which activates NOS
NOS catalyses the conversion of arginine to citrulline + NO
NO diffuses into the SM, activated guanylate cyclase to concerted GTP to cGMP causing SM cell relaxation

Question 56

Endothelial-derived factors - endothelin-1 (conversion to?by what? activators? pathway? regulate SM actions?)

Answer 56

Converted:
- into endothelin via endothelin-converting enzyme
Activators:
- thrombin
- GF
- angiotensin II
- low shear stress
Pathway:
- powerful vasoconstrictor, binds to endothelin receptors on SM (GPCR form PLC and Ca
Regulate:
- balance of endothelin prod and NO prod in endothelial cells important regulating vasc SM function

Question 57

Myogenic response in resistance arteries - Pa changes? autoregulation (definition? myogenic mechanism?) signalling mechanism for vessels?

Answer 57

Pa:
- higher Pa creates a narrow diameter of vessel
Def:
- maintenance of constant tissue blood flow when BP changes
Myogenic:
- vasc SM increases contraction when BP increases and vice versa
Mechanism:
- increased in transmural Pa
- causes depol
- act Ca chs
- increases Ca conc
- creating tension

Question 58

Cerebral circulation - sensitivity to CO2?

Pulmonary circulation - systemic and pulmonary arteries (hypoxia?)

Answer 58

Sensitivity:
- more CO2 vasodilation
- less CO2 vasoconstriction
(hypervent halved BF)
Pulmonary circulation:
- systemic hypoxia causes vasodilation
- pulmonary hypoxia causes vasoconstriction
Optimise local vent/perfusion ratio
Reduce local alveolar perfusion to match a fall in local ventilation
Diverts blood away from hypoxic alveoli to those with normal ventilation