CELL Phsyiology Flashcards

1
Q

The four broad categories of cells

A
  1. Epithelial cells
  2. Connective tissue cells
  3. Nerve cells
  4. Muscle cells
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2
Q

The phospholipids in the phospholipid bilayer are

A

Amphipathic

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3
Q

Amphipathic

A

Having a hydrophilic head and a hydrophobic tail

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4
Q

Membrane cholesterol

A
  • Found primarily in the outer cell membrane
  • Cholesterol is slightly amphipathic.
  • Functions to maintain membrane fluidity
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5
Q

Two classes of membrane proteins

A
  1. Integral membrane proteins

2. Peripheral membrane proteins

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6
Q

Integral membrane proteins

A

Embedded in the membrane or membrane spanning (so-called “transmembrane” proteins)

Amphipathic (contain polar and non-polar domains/amino acids)

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7
Q

Peripheral membrane proteins

A

Not amphipathic

Lie on membrane surface, bound to polar regions of integral proteins

Primarily on cytosolic surface

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8
Q

The three types of junctions

A
  1. Desmosomes
  2. Tight junctions
  3. Gap junctions
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9
Q

Desmosomes

A
Structural characteristics: 
- Adjacent cells separated by ~ 20 nm 
- Form “dense plaques” 
- Firm attachment between cells gives
structural integrity

Protein components:

  • Cadherins (extend into extracellular
    space and bind with cadherins from
    adjacent cells)
  • Keratin (anchors desmosome to
    cytoskeleton)
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10
Q

Tight junctions

A

Structural characteristics:

  • No space between adjacent cells - Occurs in band around entire cell
  • Common in epithelia

Protein components:

  • Complex >40 known proteins
  • Occludins
  • Claudins
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11
Q

Gap junctions

A

Structural characteristics:
- Adjacent cells separated by ~ 2-4 nm
- Form pores between cells, allowing
passage of ions and small molecules

Protein components:
- Connexins

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12
Q

Structure-Function relationship of cell membranes

A
  1. Regulate passage of substances into and out of cell (part 2)
  2. Detect chemical messengers arriving at the cell surface (part 3)
  3. Link adjacent cells together
  4. Anchor cells to extracellular matrix
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13
Q

The nucleus

A
  • Largest organelle (typically one/cell)
  • Primary function: storage of genetic information (DNA!), in the form of chromatin
  • Surrounded by membrane = nuclear envelope, with openings called nuclear pores

Nuclear pores facilitate…

  • Passage of RNA into the cytoplasm
  • Entrance of proteins that modulate gene expression
  • Contains nucleolus: site of ribosomal RNA synthesis and protein components of ribosomes
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14
Q

Ribosomes

A
  • Smallest (~20 nm) and most abundant organelle (~10 million)
  • Primary function: “protein factory”
    – translates RNA into protein
  • No surrounding membrane (comprised of proteins and RNA)
  • Critical component of the central dogma of molecular biology (Watson & Crick)

DNA&raquo_space;» RNA&raquo_space;> PROTEIN
nucleus. Ribosome

  • Found floating free in the cytoplasm or attached to endoplasmic reticulum
  • Free ribosomes primarily synthesize cytosolic proteins - Membrane-bound ribosomes primarily synthesize membrane bound proteins
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15
Q

Found floating free in the

  • Free ribosomes primarily synthesize
A
  • cytoplasm or attached to endoplasmic reticulum

cytosolic proteins - Membrane-bound ribosomes primarily synthesize membrane bound proteins

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16
Q

Endoplasmic reticulum

A

Contains SMOOTH and ROUGH ER

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17
Q

SMOOTH ER

A
  • continuous with rough ER and nuclear envelope

- Contains enzymes associated with for e.g. fatty acid synthesis. Stores and releases calcium*

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18
Q

ROUGH ER

A
  • “rough” appearance comes from
    adherent ribosomes
  • Site of protein synthesis. Proteins
    synthesized in lumen distributed to
    other organelles or secreted
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19
Q

Golgi apparatus

A
  • Structure: series of membranous sacs (“cisternae”), forming a cup shape. Polar, with a “cis” and “trans” face.
  • Function: cellular “post office”; modifies and sorts proteins arriving from the rough ER; distributes them to other organelles or to the membrane for secretion
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20
Q

Endosomes

A

Structure: small membrane-bound vesicle

Function: Sorting vesicular “traffic” in the cell.

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21
Q

Lysosomes

A
  • cellular stomach
  • acidic environment. Contains digestive enzymes

breakdown:
- damaged organelles
- engulfed bacteria
- engulfed debris form dead cells

Important for cells defence systems

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22
Q

Peroxisomes

A

Cellular “reprocessing plant”

Nueatral PH, contain oxygen consuming enzymes, generating H2O2

Breakdown:

  • fatty acids (beta-oxidation)
  • detoxification of alcohol
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23
Q

Mitochondria

A

Structure: double-membrane bound, interconnected rod-like structures. Inner membrane folded into “cristae”, giving distinct appearance

Function: “powerhouse” of the cell; transfers energy present in nutrients to adenosine triphosphate (ATP) in a process called cellular respiration

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24
Q

Three classes of cytoskeleton are

A
  1. Actin filaments
  2. Intermediate filaments
  3. microtubules
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25
Q

Actin filaments

A

G-actin form polymer of two twisting chains, forming F-actin

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26
Q

Intermediate filament

A

Twisted strands of multiple possible proteins (keratin, Desmond, laminin)

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27
Q

Microtubules

A

Hollow tubes, formed form tubular subunits

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28
Q

Does Diffusion across the membrane occur through the lipid bilayer, and/or via proteins

A

YES

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29
Q

What determines a modules ability to diffuse across the membrane

A

Polarity

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30
Q

Nonpolar molecules diffuse across membranes relatively ________ (e.g. oxygen, carbon
dioxide, fatty acids)

A

Quickly

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31
Q

Polar molecules diffuse across membranes relatively ________ (e.g. ions [K+], glucose)

A

Slowly

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32
Q

Diffusion equilibrium

A

When one compartment of high conc. And another compartment of low conc. Combine to to reach in the middle and reach an equilibrium

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33
Q

Net flux

A

The direction of the diffusion is a product of the balance between one way flux between compartments

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34
Q

The greater the surface area,

A

The greater area for diffusion to take place, therefore faster net flux

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35
Q

Large differences in

concentration will drive _______ diffusion

A

Greater

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36
Q

Different molecules diffuse at

A

Different rates

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37
Q

Large portions diffuse _____ and ions diffuse _______

A

Slow

Fast

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38
Q

Ion channels

A

Transmembrane proteins that allow for ions to diffuse across them

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39
Q

Ion channels form

A

Pores

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40
Q

The small diameter of the ion channel pores

A

Prevent larger molecules form passing through

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41
Q

Ion channel show selective permeability to specific ions,this is determines by

A

1) channel diameter
2) charge of the polypeptides
3) number of water molecules associated with ion

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42
Q

Channel gating

A

Diffusion’s of ions through ion channels is controlled

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43
Q

Three types of channel gating

A

1) ligand gated
2) voltage gated
3) mechanically gated

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44
Q

Ligand gated

A

binding of specific molecule to channel causes conformational change

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45
Q

voltage-gated

A

a change in membrane potential causes conformational change

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46
Q

Mechanically gated

A

a physical change in the membrane (e.g. stretch)

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47
Q

Transporters

A

Membrane proteins that facilitate movement across the membranes

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48
Q

Protein-mediated transport

A

Protein-mediated movement of ions, amino acids and other small molecules occurs

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49
Q

The general model for protein-mediated transport across membranes includes three steps:

A

1) Solute binding to specific site on protein surface exposed to extracellular fluid
2) Conformation change in transporter, exposing bound solute to intracellular fluid
3) Dissociation of solute from binding site into the intracellular fluid

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50
Q

Between protein0mediated transport and ion channels, which is moves 1000X more molecules

A

Ion channels

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51
Q

If ion channels are selective, are proteins mediated transporters also selective?

A

YES

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52
Q

Magnitude of flux through transporters dependent on four factors:

A

1) solute concentration
2) affinity of transporter for solute
3) numbers of transporters in the membrane
4) rate at which the transporter goes through conformational change

53
Q

Why is the rate of flux for protein mediated transport limited

A

Because cells express a certain number of transporters

54
Q

For diffusion, why is the flux into the cells limitless?

A

Because the flux into the cell is directly proportional to extra cellular conc.

55
Q

Facilities diffusion / “downhill” via membrane portion

A
  • ‘stop’ when concentration equalized

- does not require ATP

56
Q

active transport / “uphill” via membrane protein

A
  • often referred to as “pumps”

- Requires energy to overcome concentration difference

57
Q

Is protein mediated transport passive or active

A

Active

58
Q

Energy required to power active transport (protein mediated transport) can comes from two known sources:

A

1) the direct use of ATP > primary active transport

2) the use of an electrochemical gradient across a membrane > secondary active transport

59
Q

Protein-mediated transport > primary active transport

A
  • Requires ATP - “ATPase” transporters hydrolyse ATP
    1) provides energy
    2) phosphorylates protein, a covalent modulation that changes protein confirmation
60
Q

Na+/K+ - ATPase pump is primary active transport or secondary active transport ?

A

Primary active transport

61
Q

Na+/K+-ATPase pump

A
  • present in all cells
  • moves Na+ from intracellular to extracellular fluid
  • moves K+ from extracellular to intracellular fluid
  • Maintains relatively high levels of intracellular K+, and low Na+
  • Moves three Na+ ions out of the cell and brings in two K+ ions = net transfer of positive charge
62
Q

Steps for Na+/K+-ATPase pump (5 steps)

A

1) 3 sodium ions bind to high-affinity binding sites on intracellular surface of ATP-bound protein (Potassium ions will not bind to their binding sites because they are in a low-affinity state

2) Sodium binding activates ATPase activity of transporter.
Surface of protein is phosphorylated and ADP is released

3) Protein phosphorylation causes conformational change, exposing bound sodium to the extracellular environment.
Conformational changes also changes affinity for sodium, releasing it.

4) Conformational change increases affinity for potassium, which bind to the extracellular surface of the protein, triggering release of phosphate
5) Release of phosphate returns protein to original confirmation, resulting in reduced affinity for potassium and its release into the cell.

63
Q

Other examples of ion pumps that include primary active transport

A
  • Ca2+-ATPase

- H+ -ATPase

64
Q

Ca2+-ATPase

A

important in maintaining cellular calcium homeostasis, an important regulatory signal in the cell

65
Q

H+-ATPase

A

moves H+ out the cell, therefore important in maintaining cellular pH

66
Q

Secondary active transport

A

Movement of ion down electrochemical gradient coupled to transport of other (organic) molecule, such as glucose or an amino acid

67
Q

Example of secondary active transport

A
  • Sodium flows along concentration gradient into cell (“downhill”)
  • Solute pulled inside against its concentration gradient (“uphill”)
  • Cycle of steps similar to primary active transport, except no ATP consumed
  • (Maintenance of sodium’s concentration gradient depends on primary active transport)
68
Q

Endocytosis:

A

membrane envaginations enclose small volume of extracellular fluid, which are taken into the cell

69
Q

Exocytosis:

A

intracellular membrane-bound vesicles fuse with the plasma membrane
and release their contents into the extracellular fluid

70
Q

Three types of endocytosis

A

1) Pinocytosis
2) Phagocytosis
3) Receptor-mediated endocytosis

71
Q

Pinocytosis

A
  • Nonspecific
  • includes water and whatever solutes are present
  • Vesicle fuses with lysosome, where contents are hydrolyzed
72
Q

Phagocytosis

A
  • Specific (involves interaction between particle and cell surface)
  • Unique to specialized cells of the immune system (phagocytes)
  • Involves uptake of bacteria or cell debris from damaged tissue
  • Internalized vesicle called a phagosome, fuses with lysosome, where
    contents are hydrolyzed
73
Q

Receptor-mediated endocytosis

A
  • Specific and usually unique to cell function
  • Cell surface receptors recognize high-affinity ligands
  • Clustering of receptors allows selective concentration of endocytic vesicles without engulfing large amounts of extracellular fluid (as in pinocytosis)
  • Can involve the recruitment of cytosolic clathrin, forming a clathrin-coated pit, which is then internalized
  • Depending on cell-type and ligand, vesicle can have multiple fates including fusion with endosomes or lysosomes
  • Receptor is often recycled back to the cell surface
74
Q

Type of reception meditate endocytosis

A

Potocytosis

75
Q

potocytosis

A
  • Restricted to small molecules (e.g. vitamins)
  • Generates relatively small vesicles called caveolae
  • Contents delivered to the cytosol (rather than lysosomes, etc)
76
Q

Two function of exocytosis

A

1) Replaces cell surface membrane lost during endocytosis

2) Allows secretion of membrane impermeable molecules into extracellular fluid

77
Q

Epithelial cells line the

A

cavities and surfaces of vessels and organs

78
Q

apical membrane

A

Surface facing hollow organ/tube

79
Q

basolateral membrane

A

Opposite surface (typically adjacent to blood vessels)

80
Q

Two possible pathways across epithelial membrane:

A

1) Paracellular pathway (between cells) 2) Transcellular pathway (through cell)

81
Q

Paracellular pathway (between cells)

A

Movement limited by presence of tight junctions, limited to diffusion of water and small ions

82
Q

Transcellular pathway (through cell)

A
  • Utilizes processes of diffusion and protein-mediated transport just described Often involves flow against a concentration gradient, requiring ATP
83
Q

How do cells communicate with each other (intercellular communication)?

A

Receptors

84
Q

Once a cell has received a signal, it must be “processed”, this is called

A

signal transduction

85
Q

How do cells process signals (intracellular communication)?

A
  • Lipid-soluble messengers
  • Water-soluble messengers
    → second messengers
86
Q

Cells receive signals from other cells via

A

receptor proteins → Depending on the signal, receptors can be located on the outside of the cell, or inside it

87
Q

Water-soluble signal

A
  • Most common

- Bind to plasma transmembrane receptors

88
Q

Lipid-soluble signal

A
  • Can diffuse through membrane
  • Bind to intracellular receptors
  • Generally transduce signal via change in gene expression
89
Q

Ligand-receptor interactions dictate

A

cellular signaling

90
Q

Cell signaling depends on ligand-receptor interactions, including:

A

1) Specificity
2) Affinity
3) Saturation
4) Competition

91
Q

Specificity

A

The ability of a receptor to only bind a limited number of ligands

92
Q

Affinity

A

Strength of ligand binding to receptor

93
Q

Saturation

A

Extent to which receptors are bound by ligand (100% = fully saturated)

94
Q

Competition

A

Presence of other ligands which “compete” for receptor binding sites

95
Q

Competition

A

Presence of other ligands which “compete” for receptor binding sites

96
Q

___________ between ligands is the molecular basis for many drugs

A

Competition

97
Q

Intercellular signalling can be regulated at the receptor level. What’s the primary way to regulate them?

A

Primary way to regulate receptors is through their number

  • down regulation
  • up regulation
98
Q

Down-regulation

A
  • a lowering of the number of target cell receptors
  • Can occur in response to sustained high levels of signal (negative feedback)
  • Reduces cell response to frequent/intense stimulation
  • Common mechanism to down-regulate plasma membrane receptors is through
    internalization (includes receptor-mediated endocytosis)
99
Q

Up-regulation

A
  • An increase in the number of target cell receptors
  • Can occur in response to sustained low levels of signal (positive feedback)
  • Increases cell response to low-level stimulation
  • Can occur through increased insertion of receptor-containing vesicles into the cell
    membrane
100
Q

The process of signal transduction translates a signal into a

A

cellular response

101
Q

Signal transduction pathway depends

on

A

signal and receptor location

102
Q

Cellular response:

A

1) Change in membrane properties
2) Cellular metabolism
3) Secretory activity
4) Rate of proliferation/differentiation
5) Contractility or other activity

103
Q

Examples of Transduction of lipid-soluble signals

A

steroid hormones, thyroid hormone, and vitamin A

104
Q

What is transduction of lipid-soluble signals primarily mediated by ?

A

Nuclear receptors, leading to gene expression

105
Q

Transduction of lipid-soluble signals

A

1) Circulating signal diffuses from circulation across membrane into cell
2) Signal enters nucleus and binds receptor*
3) ligand-receptor complex functions as a transcription factor, changing expression (mRNA) level of target gene
4) Change in mRNA abundance effects change in protein level, leading to cellular response

106
Q

Transduction of water-soluble signals

A
  • More complex!
  • Signal transduction occurs in two phases:
    1) binding of signal to receptor (first messenger)
    2) signals generated by receptor activation (second messenger)
  • Many second messenger systems relying on phosphorylating proteins to effect change
  • Protein phosphorylation changes its structure, eliciting a response (can be
    activation or inhibition)
  • Enzymes that phosphorylate proteins are called protein kinases
  • Phosphorylation typically occurs at tyrosine reside, therefore called receptor tyrosine kinases
  • Multistep pathways can be complex…
107
Q

Examples of transduction of water-soluble signals

A
  • Examples include polypeptide hormones (e.g. insulin) and neurotransmitters
108
Q

Second messenger systems can create cascades that

A

amplify a signal

109
Q

What does the signal that’s created by second messenger systems creating a cascade allow?

A

allows signalling molecules at low extracellular concentrations to have large effects

e.g., one molecule of epinephrine can stimulate the liver to generate and release 108 molecules of glucose

110
Q

Common mechanisms of water-soluble ligand signaling

A

1) Receptors that function as ion channels
2) Receptors that function as enzymes
3) Receptors that interact with cytoplasmic kinases (called janus kinases)
4) Receptors that interact with G-proteins (aka g-protein coupled receptors)

111
Q

1) Receptors that function as ion channels

A

“Ligand-gated ion channel”

Water soluble Messenger attaches to receptor which opens the ion channel, allowing for the flow of ions, leading to the cells response

112
Q

2) Receptors that function as enzymes

A

Water soluble messenger attaches to receptor which causes tyrosine kinase to phosphorylate a docking protein, this leads to the cells response

113
Q

3) Receptors that interact with cytoplasmic kinases (called janus kinases)

A
  • Membrane receptor has no intrinsic enzyme activity, but upon activation of the receptor, an associated kinase will be turned on

Water soluble messenger attaches to receptor which causes the Janus kinase to make ATP and protein react together in a rxn, this leads to the cells response

114
Q

4) Receptors that interact with G-proteins (aka g-protein coupled receptors)

A
  • Largest group of receptors for water-soluble signals

- G-proteins “couple” receptor with effector proteins to generate second messengers

115
Q

G-proteins are

A

complex mediators of signaling through G-protein coupled receptors

116
Q

G proteins are made up of three subunits

A
  • Alpha subunit

- Beta-gamma subunit complex

117
Q

Alpha subunit

A

binds GDP/GTP

118
Q

Beta-gamma subunit complex:

A

Beta-gamma subunit complex: help anchor alpha subunit in membrane

119
Q

Receptors that interest with G-proteins

A
  • Ligand binding changes affinity for alpha subunit to GTP away from GDP
  • GTP-GDP exchange causes dissociation between alpha subunit and beta-gamma complex
  • Activated alpha subunit binds to effector protein to initiate cellular response
120
Q

Three major families of G-proteins exist:

- Defined by second messenger system they modulate and how

A
  • Gi : inhibits production of cyclicAMP
  • Gs : activates production of cyclicAMP
  • Gq : activates phospholipase C
121
Q

cAMP is a

A

potent second messenger, the levels of which are tightly regulated

122
Q

cAMP

A
  • cAMP acts by activating cAMP-dependent protein kinase (aka protein kinase A; PKA)
  • PKA has multiple targets, meaning it can elicit multiple responses in the same cell (and different response in different cells, depending on the suite of target proteins expressed)
123
Q

What is the synthesis of cAMP catalyze by ?

A

Synthesis of cAMP from ATP is catalyzed by adenylyl cyclase

124
Q

Breakdown of cAMP is catalyzed by

A

cAMP phosphodiesterase

125
Q

Can calcium act as a second messenger ?

A

YES

126
Q

How do signals cause the cytosolic Ca2+ concentration to increase?

A
  • Activation of plasma membrane Ca2+ channel (This could be by signal binding as shown, or also via a change in membrane potential in the case of a voltage-gated Ca2+ channel)
  • Opening of Ca2+ channel on the ER membrane
  • Active transport of Ca2+ out of the cell blocked by a second messenger (not shown)
127
Q

How does increased Ca2+ concentration elicit a cellular response?

A

Typically via binding to proteins and activating them, e.g. Calmodulin

128
Q

Cessation of intracellular signaling is required to prevent

A

overstimulation of the cell

129
Q

Cessation of intracellular signalling is most commonly occurs at the level of receptor activation

A
  • decreased concentration of signal (breakdown/uptake/diffusion)
  • Change in receptor conformation (e.g. via phosphorylation)
    > changes signal binding affinity
    > prevents further G-protein binding to the

receptor
- Receptor mediated endocytosis