biology and physiology Flashcards

1
Q

what are action potentials

A

Differences in ion concentrations across the nerve cell membrane provide the potential energy required to transmit nerve impulses.

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2
Q

plasma membrane potential is due to…

A

due to the separation of electrical charges across the cell membrane

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3
Q

What allows charge separation across the plasma membrane to happen

A

action of the NA=/k+ atoase activekly transporting na and k+ in different directions across the membrane

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4
Q

na/k ATpase role

A

replenish the K+ lost from the cell

remove the Na+ accumulated within the cell

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5
Q

Na+/K+ ATPase mechanism

A
  1. Binding of cytoplasmic Na+ to the protein stimulates phosphorylation by ATP.
  2. Phosphorylation causes the protein to change the conformation.
  3. The conformational change expels Na+ to the outside and extracellular K+ binds.
  4. K+ binding triggers release of a phosphate group.
  5. Loss of phosphate restores original conformation.
  6. K+ is released and Na+ sites are receptive again. The cycle repeats.

Role= replenish the K+ lost from the cell
=remove the Na+ accumulated within the cell

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6
Q

resting membrane potential

A

Due to the relatively high membrane permeability of K+.
Inside and outside the cell= electrical neutrality
Outside Na+ balanced mainly by Cl-.
Inside K+ balanced mainly by A-.
Other anions present= PO4-, Cl-

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7
Q

leak channels

A

negatively charged ions line up on the other side of the membrane

K+ leaks out

separation of charges constitues to the membrane potential

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8
Q

Electrochemical equilibrium

A

Concentration gradient tends to drive K+ out of the cell but the negative charge inside attracts K+ back in.
Equilibrium is established where the electrical potential balances the chemical potential.

chemical gradient can be balanced by an electrical potential

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9
Q

what produces chemical force and what is this equal and opposite to in order to reach equilibrium potential

A

chemical force produced by the concentration gradient

chemical force is equal and opposite to THE ELECTRICAL FORCE EXPERIENCED BY AN ION VIA A VOLTAGE

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10
Q

nerst equation

A

enrst equation describes equilibrium potential

The voltage across the membrane is proportional to the ratio of the ion concentrations on either side of the membrane.

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11
Q

goldmans equation

A

a more realistic approxmatuon of memrbane potential

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12
Q

Effect of external K+ concentration on membrane potential of skeletal muscles

A

Increase in external potasiunnion concentration increases membrane potential

Doing the log of external potassium concentration with membrane potential give a linear relationship which suggests that

Increasing extra cellular concentration depolarises the cell

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13
Q

what controls the membrane potential

A

changes in ion permeability due to opening and closing of protein ion channels in the membrane

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14
Q

neuronal signalling

A

Rapid changes in membrane potential (action potential)

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15
Q

Neuronal firing

A

Rapid depolarization caused by opening of voltage gated cation channels.

4 types of ion channels:

  • voltage gated
  • Ligand gated (extracellular ligand)
  • Ligand-gated (intracellular ligand)
  • Stress activated
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16
Q

Initiating an AP

A

Initial change in membrane potential (depolarization) is required.
Threshold comes from the opening of small capacitance ligand-gated cation channels.

(Nicotinic acetylcholine receptors at skeletal NMJ,

5HT3 receptors and P2X at CNS synapses +smooth muscle)

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17
Q

what causes the initial depolarization

A

Opening of small capacitance cation channel.

Graded responses.

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18
Q

stages of an action potential

A
  1. if local potential change;graded potential reaches the threshold potential na channels open

na channels open and influx of calcium causing depolarization

repolarization-na channel closes and efflux of potassium channels to reverse the increase in membrane potnetial

hyperpolarization-K+ channel remain open after potential reaches resting level

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19
Q

oubain

A

na/K+ atpase inhibitor

Reduces the size of the AP progressively until the membrane Na+ gradient is reduced to the point where the APs can be initiated but fail.

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20
Q

tetrodotoxin

A

blocks neuronal VGSC

abolishes AP

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21
Q

action potential refractory period is due to….

A

due to the inactivation of voltage gated na channels

during this period, another stimulus given to the neuron (no matter how strong) will not lead to a second action potential

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22
Q

Propagation of action potential along an axon. why propagation goes forward and not backwards

A

At rest the membrane is polarised.
Depolarization due to AP sets up local circuit currents in both directions.
In ‘backwards’ direction, Na+ channels are in refractory phase and another AP cannot be generated.
AP moves forward.

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23
Q

speed of conductance

A

regulated by
Temp

Axon diameter [thicker the axon, lower the longitudinal resistance, faster the conductance.]
[membranes have high capacitance= charge storage]

myelination

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24
Q

what is greater at increasing the speed of conductance myelination or increasing diameter

A

insulating the axon with myelin is a more efficient way to increasse AP conduction velocity than increasing diameter

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25
Q

Glia

A

Oligodendocytes wrap multiple CNS axons with myelin.

nn cells apply myelin to single peripheral axons.

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26
Q

saltory conductance

A

is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials.

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27
Q

local anaesthetic

A

Block conduction of APs in sensory nerves by blocking VGSC from the inside.

Weak bases. (e.g lidocaine, bupivacaine)
Need to diffuse through axon membrane and must be uncharged at plasma pH.
Charged molecular species (ionised) cannot pass back through the membrane and is trapped.
Ionised drug binds to and blocks the VGSC.

28
Q

different sensitivities to local anaesthetics

A

nerve bundles consist of multiple fibre types

myelinated and thicker axons are more difficult for LAs to treat than thin, unmyelinated axons

c fibres carrying pain singlans are easier to block than motor nerve fibres

29
Q

Applications of LAs

A

Surface anaesthesia

Infiltration

  • injection in tissues
  • adrenaline added (vasoconstrictor to prevent diffusion away from site)

Intravenous regional

Nerve block

Spinal

Epidural

30
Q

Pain

A

Unpleasant sensory and emotional experience associated with actual or potential tissue damage.
Duality. Has a physiological and psychological aspect

31
Q

Nociception

A

Neural physiological process of encoding and processing noxious stimuli.

32
Q

Nociceptor

A

Sensory neuron detecting noxious input.

Pseudounipolar neuron with a peripheral and central axon.

33
Q

a protein involved in pain

A

nav1.7

34
Q

Nociceptor nerve endings

A

Bare nerve ending.
Specialised to detect high threshold noxious stimuli (heat, cold, high threshold mechanical stimuli, capsacin)
Specific cation channels can detect these stimuli

35
Q

TRPV 1

A

Receptor for capsaicin, protons.
Detects noxious heat.

6 transmembrane ion channel with a pore forming loop.
4 subunits form the channel.
Na+ and Ca2+ cation permeable.

Opening the channel leads to ion influx.
Depolarises the membrane.

36
Q

Voltage-gated sodium channels

VGSC in the nociceptor

A

Generate action potential.

Tetrodotoxin sensitive + tetrodotoxin insensitive

37
Q

Tetrodotoxin insensitive

A

Nav1.9, Nav 1.9
Nav1.8= highly expressed in nociceptors (nociceptor specific)

Role in acute noxious mechanical sensation
Important in acute cold sensation.
Doesn’t inactivate in low temp whereas all other Nav channnels do.

38
Q

Sensory nerve and nerve fibres

A
  1. Nociception
    A-delta fibres= Lightly myelinated, medium diameter

C fibres= unmyelinated, small diameter

  1. Proprioception, light touch
    A-beta fibres= myelinated, large diameter
39
Q

Nociceptor central terminal

A

Main excitatory transmitter= Glutamate
Substance P
VGCC= facilitate transmitter release

Various receptors on the presynaptic terminal modulate transmitter release= GABA, CB1, DOR, MOR

40
Q

synaptic transmission. ampa receptor

A
AMPA receptors
Glutamate released presynaptically binds to AMPA receptors at the postsynaptic neuron(second order neuron that is located at the dorsal horn).
Ligand gated ion channels.
Primarily Na+ gating and depolarising.
Fast excitatory transmission.
41
Q

Nociceptor connections in the spinal cord

A

-Projection neurons (direct connection to brain)
Nociceptor specific= only receive input from nociceptors (A-delta, C fibres)

Wide dynamic range= receive input from nociceptor (A-delta, C fibres) and non-nociceptors (A-beta)

-Various types of interneurons
Inhibitory= GABA
Excitatory= Glutamate

42
Q

Modulation of nociceptor signalling: mu-opioid receptor

A

Localised presynaptically.
Central terminal.

Modulation of ion channel function.
Results in reduced synaptic transmission.

43
Q

Acute MOP receptor function

A

Inhibition of adenylyl cyclase and reduction in cAMP.
Increase opening K+ channels and hyperpolarization.
Decrease opening of Ca2+ channels.
Reduced neuronal excitability.

44
Q

Endogenous inhibitory controls: inside the dorsal horn

A

nhibitory interneurons in the dorsal horn: GABA transmission

GABA A receptor= ligand gated ion channel
Localised presynaptically of the nociceptor terminal
Agonism
Cl- gating, hyperpolarises the membrane and dampens excitation.

45
Q

Acute nociceptive pain

threshold of activation and when activated

A

Pain= sensation of hurt
Nociception= detection of noxious stimuli
Leads to Reflex or Pain

Threshold of activation is high.
Under normal circumstances, the nociceptive system is not activated.
Warning device.
Protective mechanism (reflex, avoidance behaviour)

46
Q

Hypersensitivity

A

Inflammation sensitizes the sensory system.
Innocuous stimuli elicit pain and the response to noxious stimuli is enhanced and prolonged.

Helps to protect and preserve by provoking avoidance of further contact with such stimuli.
Aids healing and repair.
Adaptive process.

47
Q

hypersensitivity occur due to

A

Occur as a consequence of neuronal damage.

  • Mechanical trauma
  • Metabolic disease such as diabetes
  • Neurotoxic chemicals= chemotherapy
  • Infection
  • Tumour invasion
  • Spinal cord injury
  • Stroke
48
Q

Allodynia

A

Pain in response to normally innocuous stimulus

49
Q

Hyperalgesia

A

Pain in response to a noxious stimuli with an exaggerated response

50
Q

Classification of nociceptive, inflammatory and neuropathic pain

in terms of 
pain sensitivity (threshold)
stimulus
clinical setting
function
A
Nociceptive pain=
High threshold
Noxious stimuli
Acute trauma
Protective
Inflammatory pain=
Low threshold
Inflammation
Post operative pain, Arthritis
Healing/ repair
Neuropathic pain=
Low threshold
Neural damage and ectopic firing
PNS and CNS lesions, Diabetic neuropathy, Trigeminal neuralgia
Pathological
51
Q

changes in the nociceptive system can be what two types of sensitisation

A

peripheral

central

52
Q

peripheral sensitisation

A

nociceptor activation threshold are lowered

the nociceptor starts firing more and more and this is experienced as pain

53
Q

Central sensitisation

A

Spinal cord pain neurons are changed (anatomically, physiologically).
Show increased responsiveness to peripheral input

54
Q

Tissue damage and inflammation

A

inflammation-associated changes in the chemical environment of the nerve fiber
Thus, tissue damage is often accompanied by the accumulation of endogenous factors released from activated nociceptors or non-neural cells that reside within or infiltrate into the injured area (including mast cells, basophils, platelets, macrophages, neutrophils, endothelial cells, keratinocytes, and fibroblasts).

55
Q

how do these factors (inflammaotry soup)released from nociceptors during tissue damage work

A

Nociceptors express receptors that can recognise these factors.
Factors bind to the receptor.
Leads to depolarisation or alteration of the activation threshold.
Nociceptor excitation.

56
Q

prostalgladin sensitisation pathway

A
Prostaglandins produced from arachidonic acid in several steps, including COX enzyme activity.
Prostaglandin E2 binds to PGE2 receptor.
Activates Gs G-protein
Activates adenylyl cyclase.
Converts ATP into cyclic AMP.
Cyclic AMP activates protein kinase A.
Facilitates voltage-gated sodium channels.
Changes nociceptor excitability.
57
Q

NGF altering gene expression

A

NGF(nerve growth factor) produced by mast cells and fibrolasts

alters gebe expressions of other receptors that can induce nociceptor excitability

58
Q

receptor for NGF

A

TrkA

59
Q

Protons activate ASICs. what are ASICs

A

ASICs (acid sensitive ion channels)
Family of 2T channel subunits.
Homo and heterotrimers.

Na+ gating and depolarising

60
Q

ASICs and pain

A

activated by small changes in pH

ASIC3 can be inhibited by a peptide toxin from the venom of the sea anemone

snakes toxin inhibits pain axis

61
Q

p2x and atp

A

p2x is a ligand gated ion channel that recognises ATp

cation gating and depolarization
direct excitation of nocieptor

62
Q

p2x structure

A

heteromultimers of subunits consisting of 2T1P

63
Q

Bradykinin sensitization pathway

A

Bradykinin binds to the Bradykinin receptor on nociceptor terminal.
Activates Gq G-protein
Activates phospholipase C-beta
Converts membrane phospholipid PIP2 into DAG and IP3.
DAG activates the Protein Kinase C-epsilon isoform.

Bradykinin increases the response of TRPV1 to heat.
Reduces the thermal activation threshold of TRPV1.

64
Q

how do we get an increase in synaptic strength

A

increase of presynaptic e.g. calcium channels after nerve damage
loss of mu opioid receptors on presynaptic terminal after nerve damange

increase of postsynaptic signalling via nmda receptors

65
Q

somatosensory cortex

A

location, duration and intensity

involved in the perception and modulation of pain

spinal cord. medulla, mid brain, thalamus. s1, s2

66
Q

nociceptors

A

alpha delta

c fibres

67
Q

non nociceptor

A

alpha beta