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Physiology with pharmacology - L1 > Cells > Flashcards

Cells Flashcards

(transport, communication & signaling)

1
Q

Which is easier to transport across cell membrane?
Glucose, H20, Na+, Steroid hormones, O2

(easiest to hardest)

A

O2, steroid, H2O, glucose, Na+

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2
Q

What are 2 types of passive transport?

A

Simple diffusion & Facilitated diffusion

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3
Q

What are 2 types of active transport?

A

Primary (direct) & Secondary (indirect)

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4
Q

What 2 factors can determine level of transport into a cell?

A

Concentration gradient & voltage gradient

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5
Q

What type of charged ion is more likely to be able to enter a cell?

A

positively charged ion

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6
Q

What type of solute can move straight through the lipid bilayer?

A

UNCHARGED hydrophobic solutes

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7
Q

What is an example of a uncharged hydrophobic solute?

A

CO2

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8
Q

Describe “Jx = Px ([X] - [x]o)”

A

Flux = Permeability x difference in concentration (between ECF & ICF)

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9
Q

What is required to transport hydrophilic solutes?

A

Transmembrane proteins

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10
Q

Describe the structure of integral membrane proteins (3 points)

A
  • a-helical domains
  • can pass through membrane multiple times
  • Termini (end) may be cytoplasmic or extracellular
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11
Q

What are 4 types of transmembrane proteins?

A
  • Pore (non-gated channels)
  • Channel (gated pore)
  • Carrier
  • Pump (subtype of carrier)
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12
Q

What is the use of transmembrane proteins?

A

Provide solutes with a ‘solute permeation pathway’

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13
Q

Describe the hydrophilic permeation pathway created by transmembrane proteins.

A

Made up of amphipathic helices - alternating hydrophobic amino acids.
- hydrophobic surfaces face the lipid membrane
- hydrophilic surfaces create a central pore

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14
Q

What type of transport do pores allow?

A

Passive transport

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15
Q

What is the driving force for movement in pores?

A

Electrochemical gradient

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16
Q

Describe the properties of pores (2 points)

A
  • always open
  • multiple subunits
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17
Q

What is an exampled of a pore?

A

Aquaporins

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18
Q

What do channels allow for?

A

Facilitated diffusion

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19
Q

What is the driving force for movement in channels?

A

Electrochemical gradient

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20
Q

Describe the properties of channels (2 points)

A
  • gated ion channel
    multiple subunits
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21
Q

What is an example of a channel?

A

Potassium channel

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22
Q

What are 3 types of channels?
(think gated)

A
  • voltage-gated
  • ligand-gated
  • mechanical-gated
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23
Q

What are the 2 types of ligand-gated channels?

A
  • Intracellular ligand
  • Extracellular ligand
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24
Q

What 4 parts does a channel have?

A
  • a moveable gate
  • a sensor (can sense: voltage, ligand, mechanical)
  • a selectivity filter
  • an open channel pore
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25
Q

Do carriers have a continuous transmembrane path?

A

NO

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26
Q

Describe the time taken of Carrier-mediated facilitated diffusion vs normal diffusion.

A

Carrier-mediated facilitated diffusion is slower

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27
Q

Carrier-mediated facilitated diffusion can become saturated. What factors can limit the flux (Jx)? (2 Points)

A
  • Number of carriers in the membrane
  • Speed by which carrier can cycle through steps and become ready for next substance.
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28
Q

Briefly describe steps of Carrier-mediated facilitated diffusion

A
  1. Carrier open
  2. X binds at binding site
  3. Outer gate shuts (X is ‘occluded’ inside protein)
  4. Inner gate opens
  5. X enters inside of cell
  6. Inner gate closes (nothing is ‘occluded’)
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29
Q

What is the driving force for movement in carriers?

A

Electrochemical gradient

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30
Q

What do carriers use to mediate active transport? (3 things)

A
  • Pumps
  • Cotransporters
  • Exchangers
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31
Q

Examples of substances travelling against their gradient

A
  • ions for neural communication
  • uptake of glucose
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32
Q

What is the difference between primary & secondary active transport?

A

Primary:
- uses pumps - driving force = chemical reaction e.g. ATP hydrolysis.

Secondary:
- uses cotransporters & exchangers - driving force = uphill movement one of solute with the downward movement of another solute.

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33
Q

Give an example of a pump

A

Na+ - K+ ATPase

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34
Q

What is the difference between cotransporters & exchangers?

A

Co-transporters - move solutes in same direction
Exchangers - move solutes in opposite direction

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35
Q

What is the common example that is often found to cause the movement of solutes using cotransporters & exchangers?

A

The inward Na+ electrochemical gradient

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36
Q

What is another name for cotransporter?

A

Symporters

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37
Q

What is another name for exchanger?

A

Antiporters

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38
Q

What did the discoveries into cell communication lead to?

A

Concepts of chemical mediators & receptors

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39
Q

What is pilocarpine? (2 effects)

A

Poison that:
- increases saliva secretion
- decreases heart rate

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40
Q

What drug can inhibit the action of pilocarpine?

A

Atropine

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41
Q

What was concluded after discovering that atropine inhibits the actions of pilocarpine?

A

They both must act on a common target.

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42
Q

Who discovered acetylcholine as a chemical mediator?

A

Otto Loewi & Henry Dale

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43
Q

What did Loewi discover about acetylcholine?

A

It is an agent used in the chemical transmission of nerve impulses (neurotransmission)

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44
Q

Briefly outline the steps to Loewi’s experiment (acetylcholine)

A
  1. Stimulate vagus nerve
  2. Collect fluid
  3. Inject into denervated heart
  4. Slowed heart rate
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45
Q

What is another phrase for chemical mediators?

A

Extracellular signal molecules

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46
Q

What are broad examples of chemical mediators?

A

Hormones & Neurotransmitters

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47
Q

Describe briefly the process of cell signaling

A

Chemical mediators bind to receptors on target cells. This initiates intracellular signals that alter cell behaviour through effector proteins.

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48
Q

What is signal transduction?

A

Process of converting an extracellular signal to an intracellular signal

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49
Q

What is a mediator?

A

A chemical, peptide or protein that conveys information from one cell to another.

50
Q

When is a mediator released?

A

In response to a stimulus.

51
Q

What is the purpose of having multiple receptors use similar transduction mechanisms?

A

Allows for coordinated responses & amplification of signaling.

52
Q

What is the criteria that establishes a substance as a mediator? (3 Points)

A
  • able to produce biological action within an appropriate time frame.
  • application of authentic sample reproduces the biological effect.
  • Inteference with synthesis, release or action ablates biological response.
53
Q

What are the 5 main types of intercellular communication?

A
  • Contact-dependent
  • Paracrine
  • Synaptic
  • Endocrine
  • Autocrine
54
Q

Where can signals act?

A
  • locally
  • over long distances
55
Q

What can signals vary in?

A
  • Speed
  • Selectivity
56
Q

Describe autocrine communication

A

Releases and mediator that will act on itself.

57
Q

Describe the range of contact-dependent communication

A

Shortest (literally in contact) with target cell.

58
Q

Where is contact-dependent communication common? (2 Points)

A

Development & Immune responses

59
Q

What is contact-dependent communication?

A

Where the signaling cell comes into direct contact with the target cell.

60
Q

What is paracrine communication?

A

The release of mediators that act on other target cells locally.

61
Q

Describe how mediators used in paracrine communication are stored

A

Either stored in in vesicles or synthesized on demand.

62
Q

What are 3 examples of substances that use paracrine communications?

A
  • histamines
  • nitric oxide
  • prostaglandins (eicosanoids)
63
Q

What specialized structures are used in neuronal signaling

A

Synapses

64
Q

Describe what type of cells synapses target

A

Specific target cells that can be short or long distances from the cell body

65
Q

What are the chemical mediators used in neuronal communication called?

A

Neurotransmitters

66
Q

What are 2 examples of neurotransmitters?

A
  • acetylcholine
  • noradrenaline
67
Q

Where does acetylcholine & noradrenaline act on?

A

On the heart

68
Q

Describe the speed of neuronal signaling

A

Fast

69
Q

What is endocrine signaling?

A

Communication in which signaling mediators are secreted into bloodstream - hormones.

70
Q

Describe the length and time of endocrine communication

A

Long distances and therefore very slow

71
Q

Is endocrine communication specific?

A

No

72
Q

What forms can hormones come in?

A
  • a protein e.g. insulin
  • amino acid derived e.g. epinephrine
  • a steroid e.g. estradiol
73
Q

What are 2 methods of chemical mediator synthesis?

A
  • synthesis of smaller molecules regulated by specific molecules
  • synthesis of peptides regulated by transcription
74
Q

What are 2 types of chemical mediators?

A
  • pre-formed mediators that are stored in vesicles & released by exocytosis (rapid)
  • on-demand mediators, released by diffusion (slow)
75
Q

What did early studies into neuromuscular junctions lead to the discovery of?

A

Existence of ‘packages’ of neurotransmitters.

76
Q

What are the 2 parts of neuromuscular junctions?

A

motor nerves + skeletal muscle

77
Q

How was the experiment into the quantal hypothesis (prediction of existence of vesicles) carried out??

A

Calcium was removed from a neuromuscular junction.

78
Q

Other than removal of calcium, what other experiment was carried out to identify packages in neurons as vesicles?

A

The use of electron microscopy to view exocytosis.

79
Q

How are neurotransmitter actions terminated?

A
  • Enzymes (acetylcholinesterase at the cholinergic synapse breaks down acetylcholine).
  • Uptake of neurotransmitters back into the neurone (or supporting cells e.g. glia)
80
Q

What is a ligand?

A

A molecule that binds to a receptor (may be an agonist or antagonist).

81
Q

What is an endogenous agonist?

A

Chemical mediators, from WITHIN the body, that PRODUCE a response.

82
Q

What are receptors?

A

Macromolecules that are recognition sites for neurotransmitters, hormones etc, that allow for cell-cell communication.

83
Q

What is a benefit of knowing the function of a receptor?

A

Allows us to predict physiology.

84
Q

How are receptors classified?

A

Based on structure into classes or superfamilies.

85
Q

What are the types of receptors? (how many?)

A

4 receptors:
- ligand-gated ion channels (ionotropic receptors)
- G protein-coupled receptors (GPCR) (metabotropic receptors)
- Kinase-linked receptors
- Nuclear (intracellular) receptors

86
Q

Ligand-gated, GPCR & Kinase receptors all have 3 common features - what are they?

A
  • contain TRANSMEMBRANE segments (through hydrophobic amino acids)
  • contain LIGAND-BINDING DOMAIN (usually extracellular)
  • ligand are HYDROPHILIC (can’t cross cell membrane).
87
Q

Describe the structure of nuclear receptors

A
  • contain MULTIPLE DOMAINS
  • ligand are HYDROPHOBIC (can cross cell membrane)
  • acts as TRANSCRIPTION FACTORS.
88
Q

What is an example of a nuclear receptor?

A

Steroid hormone receptors, including oestrogen receptors

89
Q

What type of chemical mediator use ligand-gated ion channels & GPCR receptors?

A

Small molecules e.g. amino acid derived neurotransmitters.

90
Q

What type of chemical mediator use GCPRs?

A

Peptide hormones

91
Q

What type of chemical mediators use kinase-linked receptors?

A

Cytokines & peptide hormones

92
Q

What type of chemical mediator uses nuclear receptors?

A

Steroidal hormones

93
Q

What can occur as a result of the binding of a ligand?

A

A conformational change, leading to an intracellular signal or secondary messenger being generated.

94
Q

Describe the times for the different receptors

A

Ligand-gated ion receptors - milliseconds.
GPCR - seconds
Kinase-linked receptors - hours
Nuclear receptors - hours

95
Q

What are 4 cellular effects of receptor activation?

A
  • Hyper-polarisation/depolarisation = electrical signals e.g. triggering exocytosis
  • Ca2+ release = allows contractility & muscle movement
  • Protein phosphorylation - changes in enzyme activity
  • Protein synthesis - e.g. more channels inserted into the cell membrane.
96
Q

Describe the brief structure of endogenous agonist

A
  • 5 subunits (from a central aqueous pore)
97
Q

What happens to a channel when there is an agonist binding?

A

Channel is open

98
Q

What happens to a channel when an agonist is removed?

A

Channel closes

99
Q

What are 2 ways a channel can become closed? (in reference to receptors)

A
  • agonist is no longer bound
  • receptor enters a ‘desensitized’ state.
100
Q

How does the opening of a ligand-gated ion channel lead to excitation?

A
  • the opening of a channel leads to an influx of ions into the cell.
  • this changes the potential of the cell.

(activation of ionotropic receptors by excitatory neurotransmitters - membrane depolarization (more positive) - action potential firing)

101
Q

What is a nAChR?

A

Nicotinic Acetylcholine receptor

102
Q

Describe how the opening of ligand-gated channels can cause inhibition

A
  • Activation of ionotropic receptors for inhibitory neurotransmitters
  • membrane (hyper-polarisation)
  • reduces action potential firing.
103
Q

What is an example of a receptor which causes excitation?

A

nAChR (nicotinic acetylcholine receptor)

104
Q

What is an example of a receptor which causes inhibition?

A

GABA

105
Q

What makes ion channels specific to different ligand and ions?

A

The protein subunits make them different when being identified.

106
Q

How many times does a GPCR span though a membrane?

A

7 times (7 transmembrane domains)

107
Q

How do GPCR regulate effect proteins?

A

Via HETEROTRIMERIC GTP-binding protein

108
Q

What is the heterotrimeric GTP-binding G protein made of?

A
  • 1 alpha subunit
  • 1 beta subunit
  • 1 gamma subunit
109
Q

How many types of G-proteins are there?

A

20

110
Q

What are examples of effectors, whose function can be changed, as a result of G proteins?

A
  • ion channels
  • enzymes - adenylyl cyclase & phospholipase C (enzymes that are membrane bound)
111
Q

What can modulate adenylyl cyclase?

A

G proteins

112
Q

What stimulates an increase in Adenylyl cyclase?

A

Ga(s) - stimulators

113
Q

Describe the process by which Ga(s) leads to an increase in PKA (protein kinase A)

A

Binding of Ga(s):
- increase in Adenylyl cyclase
- increase in cAMP
- increase in PKA

114
Q

What causes an decrease in Adenylyl cyclase?

A

Ga(i) - inhibitory

115
Q

Describe the process by which Ga(i) leads to a decrease in PKA (protein kinase A)

A

Binding of Ga(i):
- decrease in adenylyl cyclase
- decrease in cAMP
- decrease in PKA

116
Q

What is cAMP

A

a secondary messenger

117
Q

What is the role of Ga(q)?

A

Increases intracellular calcium through the enzyme phospholipase C

118
Q

What subunit mediates Ga(s)?

A

alpha

119
Q

What subunits mediates Ga(i)?

A

alpha, beta & gamma (only alpha involved in adenylyl cyclase inhibition)

120
Q
A
121
Q

What subunit mediates Ga(q)?

A

alpha

Physiology with pharmacology - L1 (17 decks)

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