Physiology > Cell physiology > Flashcards

Cell physiology Flashcards

need to do karl swan stuff (75 cards)

Study These Flashcards
1
Q

why do cells try to have a low intracellular calcium concentration?

A

because too much calcium causes a toxic effect and calcium phosphate salts are poorly soluble so they will precipitate in cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the historical milestones in calcium signalling?

A
  1. Sydney ringer used isolated frog hearts and put buffer made with normal water (ions in) and made them contract but didn’t with distilled water
  2. Lewis Heilbronn discovered that frog muscle contracted when Ca2+ was applied to the cut end
  3. Roger Tsien developed a method to measure calcium concentration inside cells and trap Ca2+ fluorescent indicators inside a cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is a fascicle?

A

a bundle of muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where is a dihydropyridine/ L-type receptors found?

A

on the t-tubules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

where is a ryanodine receptor found?

A

on sarcoplasmic reticulum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what does ATP always need?

A

Mg2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is RGS14?

A

a regulator protein of G-protein signalling 14 which acts as a signalling scaffold in the brain and other tissues to integrate different pathways
- plays a role in synaptic plasticity and learning and memory by inhibiting signalling pathways in areas like the hippocampus
- contains multiple domains that allow it to bind to various proteins including active and inactive G-proteins and small GTPases like H-ras
- regulates calcium signalling in Ca2+ neurones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what did cells lacking RGS14 show?

A

They had smaller calcium peaks from glutamate uncaging
- - RGS14 regulates calcium signalling in CA2 neurons
- Ca is important in RGS14’s role in restricting plasticity of dendritic spines
- Ca neurons may resist plasticity to help encode specific types of memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is protein kinase C activated by?

A

DAG and Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are common secondary messengers?

A

IP3, DAG and Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

when do calcium levels go from resting level to activated level?

A

when depolarisation causes Ca channels to open due to ligand binding to receptor. second messenger transmits signal to receptors on ER/SR so they open and Ca is released from ER to cytosol
- so Ca release into cell by voltage-gated channels or from SR increases cytosol conc of Ca2+ so cell is activated and role can be performed
- THEN Ca needs to be removed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the 3 methods that cells maintain a low cytosolic Ca2+ using 3 methods?

A
  1. Remove Ca2+ out of the cell
  2. Sequestering (set apart or isolate) calcium into intracellular stores
  3. Chelating calcium - calcium binding to calcium binding proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how can cells maintain a low cytosolic Ca2+ by removing Ca2+ from the cell?

A

with help of plasma membrane calcium ATPases (PMCA)
or by sodium/calcium exchangers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

with help of plasma membrane calcium ATPases (PMCA)
or by sodium/calcium exchangers

A

sense high Ca and take it out of the cell
needs ATP from mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how do sodium/calcium exchangers work?

A

removes and exchanges Ca for Na
- v powerful, can sort out 2000 ca2+ per second

NCKC - Ca and K out, 4Na in
NCX - Ca out, 3Na in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how can cells maintain a low cytosolic Ca2+ sequestering Ca2+ into intracellular stores?

A

SERCA pumps
Uniporters - MCU (mitochondrial calcium uniporter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how much Ca2+ can the SR and ER store up to?

A

1/2mM (half a millimole)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

other than ER and SR, where can calcium be stored?

A

nuclear envelope, endosomes, lysosomes and mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the 2 families of intracellular ca2+ release receptor channels that the ER has?

A

inositol triphosphate receptor (IP3Rs) and ryanodine receptor (RyRs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how do SERCA pumps work?

A
  • Sarco(endo)plasmic reticulum calcium ATPase pumps
  • ER intracellular ca2+ release receptor channels IP3Rs and RyRs sense stimulation and open the pore so calcium is released from the cytosol into the ER/SR but SERCA pumps take up Ca2+ using ATP
  • 2Ca2+ in and 3H+ are pumped out of the ER for every ATP hydrolysed by changing conformation from E1 to E2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the details of SERCA with conformational changes?

A

SERCA has 2 main conformations:
- Starts in E1 where ions are held closer to the cytosol than the ER/SR lumen so ions binding sites are facing cytosol (called E1 state) with 3 protons which need to be displaced by 2Ca2+ and 3H+ are released into cytsol
- Then SERCA becomes E1-2Ca2+ state
- ATP binds to E1-2Ca2+ which makes it E1-ATP-2Ca2+ state
- Then ATP gets hydrolysed so only one phosphate is attached to SERCA, ADP goes off, then its called E1P-2Ca2+
- This phosphate triggers a conformational change so binding sites move closer to ER lumen side
- Now in E2 conformation state
- Now SERCA prefers to be bound to protons than calcium so calcium goes off into ER lumen and 3 protons bind again so it goes to E2-P bc its still bound to phosphate (protons not acknowledged tho rude)
- Then phosphate removed and its just E2 conformation
- So now there’s no phosphate, it wants to go back to original conformation so binding sites move back to cytosol side so protons are facing cytosol- so now back to E1 state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is the ligand for IP3Rs?

A

IP3 (cleaved by PLC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the ligand for RyRs?

A

indirectly = cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
how does the mitochondrial calcium uniporter work?
- Is in inner mitochondrial membrane - When Ca is in, it immediately stimulates production of ATP bc ATP production is calcium dependent - Ca doesn’t stay for a long time in the matrix, its removed by calcium exchanger (NCX) back to cytosol - So mitochondria is a sponge
26
which buffers can be used to chelate calcium (calcium binds)
calbindin and calsequestrin
27
where is calbindin?
in the brain
28
where is calsequestrin?
in the ER/SR
29
which sensors can be used to chelate calcium?
C2 protein domains Calcium-binding proteins with EF hands
30
what do C2 protein domains do?
allow calcium to bind directly e.g PLC, PI3K and PKC
31
do sensors like C2 protein domains undergo a conformational change?
No but calcium-binding proteins with EF hands do
32
what is an example of Calcium-binding proteins with EF hands?
calmodulin
33
what are EF hands?
calcium binding motifs for intracellular signalling - each motif consists of 12-residue loop flanked by 2 x 12 residue alpha helices, forming a helix-loop-helix structure (so 12 amino acid loops between 2 alpha helices) - E and F stand for the 2 alpha helices flanking the calcium-binding loop - the loop binds calcium ions in a pentagonal bipyramidal configuration - when Ca2+ binds, it causes a conformational change in the EF hand which can activate or inactivate the proteins function
34
how do calmodulin and troponin C work?
act as calcium sensors by translating changes in intracellular calcium levels into specific cellular responses - Used in muscle contraction, cell cycle regulation, vision and immune response
35
how does calcium activate skeletal muscles?
- L-type channels (a calcium channel - alpha1S) on the plasma membrane gets activated by depolarisation when AP comes so then a small amount of Ca2+ comes into cell - the L-type channel is located very close to the RyRs which can sense when there's a conformational change in the L-type channel - RyRs also sense calcium in the cell so it is opened and calcium is released from SR - Ca2+ then activates troponin C -> muscle contraction - Ca2+ also binds to calmodulin which (through a phosphorylase) metabolises glycogen into glucose and also for the production of ATP needed for contraction
36
how does calcium activate neurones?
1. N/PQ type channels 2. NMDA receptors 3. mGluR1 glutamate receptors 4. L-type channels (calcium channels)
37
how do N/PQ type channels work in neurons?
- they are voltage gated and activated with depolarisation of the membrane when AP comes - Ca2+ goes in and triggers exocytosis of membrane - normally at synaptic endings for movement of neurotransmitters
38
how do NMDA (N-methyl-D-aspartate) receptors work in neurons?
- calcium channels that are activated by glutamate neurotransmitter
39
how does the mGluR1 glutamate receptor work in neurons?
it is stimulated by glutamate transmitter to produce inositol-1,4,5-triphosphate - this activates InsP3 receptors which release calcium through ER
40
how do L-type channel work in neurons?
- L-type channels (a calcium channel) on the plasma membrane get activated by depolarization when AP comes - Small amount of Ca2+ comes through - L-type channel is located very close to RyRs so RyRs can sense when theres a conformational change in the L-type channel - RyRs also senses calcium in the cell so it is opened and calcium is released from SR - Ca2+ then activates Troponin c --> muscle contraction - Ca2+ also binds to calmodulin which (through a phosphorylase) metabolises glycogen into glucose and also for the production of ATP needed for contraction
41
what are the synaptic effects that happen in neurons due to Ca2+ being released?
- linked to long term potentiation (LTP) - long term depression - learning and memory
42
what are the nuclear effects that happen in neurons due to Ca2+ being released?
gene transcription which also links to learning and memory
43
what is long term potentiation?
persistent strengthening of synapses based on recent patterns of activity, which increases signal transmission between 2 neurons, occurs after high-frequency stimulation, key for learning and memory
44
what are non-excitable cells?
no voltage sensitive Ca2+ channels e.g pancreatic acinar cells
45
how does calcium activate neurones?
- muscarinic receptor type 3 (an acetylcholine receptor) - CCK1 receptor ( a cholecystokinin receptors) THEY BOTH USE GPCRs
46
how do muscarinic receptor type 3 work? (acetylcholine receptors)
when these receptors are activated, they are coupled to G-proteins - this activates PLC - produced Ins(1,4,5)P3 which activates InsP3R receptor on ER and calcium is released from ER
47
how does CCK1 receptor work? (a cholecystokinin receptor)
when these receptors are activated they are coupled to G proteins - this activates ADP ribosyl cyclase which is responsible for production of an AGP and cyclic AGP ribose which are linked to activation of Ryanodine receptor channels - so calcium is released from ER
48
what does calcium release from ER trigger in pancreatic acinar cells?
enzyme secretion from pancreatic cells and fluid secretion (pancreatic juices - H2O and ions) - like digestive enzymes for food digestion
49
how are physiological calcium spikes local in pancreatic acinar cells?
1. Ca2+ spike invitation sites are concentrated in secretory granule area - mitochondria restricts calcium waves to occupy others areas of cell but also provide ATP necessary for secretion 2. secretory granule area is surrounded by mitochondria, which take up Ca2+ during calcium release - Mitochondria take in excessive calcium from granules into matrix and slowly rerelease it Quickly spread over the cell --> global response - Dangerous for cells bc calcium stays in one area for a long time and becomes toxic - Cell morphology defines Ca2+ signals
50
how does high doses of agonist (Ach) induces global Ca2+ response ?
- adding Ach, signal generates in granular area but quickly spreads all over cell which is a global response - dangerous bc calcium stays there for along time which is toxic
51
3 ways non-excitable cells replenish ER when they don’t have voltage-gated channels?
1. By the store - store operated Ca2+ entry (SOCE) 2. By canonical transient potential receptor protein channels (TRPC)
52
how does the store-operated Ca2+ entry (SOCE) work?
operated by the lumen of ER - if reduction of Ca2+ in ER, there is a direct response requirement of calcium entry from outside - direct response requirement is arranged by several molecules: - STIM1 (stromal interaction molecule 1) which goes through membrane of ER and feels calcium content with its EF hands - If ER is full, then STIM1 is happy but if not then it rises with other neighbouring STIMs to pull the SR/ ER membrane towards the plasma membrane in the area where calcium enters - Calcium entry channels such as Orai1/CRAC channel (calcium-release activated calcium channel) are in plasma membrane - When STIM1 binds to Orai1, then calcium channel is open and calcium can be replenished into ER through the SERCA pump - So Orai1 is the pore forming the subunit of the CRAC channel - Then when replenished, bond with STIM1 breaks and goes back to normal position
53
What is Orai1?
the pore forming the subunit of the CRAC channel - binds with STIM1
54
what is STIM1?
stromal interaction molecule 1, which goes through membrane of ER and feels calcium content with its EF hands
55
how does the canonical transient potential receptor protein channel (TRPC) work?
- through protein channels which can be expressed alone – truly TRPC channels - or expressed with Orai1 to improve calcium entry if needed - so STIM1 binds to TRPC channels too in the SOCE way
56
why are excitable cells greedy?
- greedy and also express SOCE - and calcium entry channels like Orai, CRAC and TRPC
57
excitable cells vs non-excitable cells
excitable - calcium entry to replenish stores is first event of stimulation!!!!!!!!! - then causes ryanodine receptor to open and then calcium release - then trigger contraction - uses voltage-activated calcium channels Non-excitable neurons - depolarization first and opening of calcium voltage gated channels where pore opens and calcium enters the cell - calcium entry is the late event after stimulation - then causes ryanodine receptor to open and then calcium release - uses IP3 channels - non-excitable cell has to be stimulated with an agonist e.g stimulus like neurotransmitter or hormone which transmits intracellular signal to IP3 and then to its receptor and then calcium release - opening of ER triggers Orai/CRAC channels or TRPC to let calcium back in
58
what are the recent calcium discoveries?
SOCE are important and linked with cancer – metastasis - Trying to produce blockers to prevent unwanted calcium entry - SOCE found to regulate cancer cell migration, invasion, metastasis - Ca2+ signalling remodelling in disease: heart, neural disorders, and acute pancreatitis - Covid-19 – SARS-COV spike protein (S1) --> induces Ca2+ signals in pancreatic stellate cells - These release cytokines like IL-18 which activates macrophages --> cytokine storm - Can prevent this by Orai1/CRAC blockers suppress Ca2+ signals --> potential therapy for inflammation and acute pancreatitis (under trial)
59
what are protein kinases?
enzymes that add phosphate groups (phosphorylation) using ATP --> regulates protein activity (turns proteins on/off) - Use ATP and it is converted to ADP and the phosphate gets stuck to the kinase to phosphorylate the protein
60
what protein phosphorylases do?
- Protein phosphatases remove phosphate groups (dephosphorylation)
61
what other ways can proteins be changed?
Methylation and acetylation also changes proteins
62
what are the types of kinases?
- Serine/threonine kinases (e.g most PKA, PKB, PKC) (more than 90%) - Tyrosine kinases - No charge on these before and then they get a negative charge added which changes their activity (PO34-) from the phosphate
63
what do receptor tyrosine kinase do?
often receptors for growth factors and oncogenes, for growth and proliferation,
64
what can PK inhibitors be used for?
anti-cancer drugs
65
what are receptor tyrosine kinases activated by?
hormones/growth factors
66
what do tyrosine kinases cause?
phosphorylation cascades (When proteins bind to each other they can activate) - Effects occur within minutes to hours - Normally phosphorylate each other on receptors
67
what are mitogen activated protein kinases (MAPK)?
kinases that have a double phosphorylation - what stimulates these is another kinase which is stimulated by another kinase - a kinase cascade
68
what are mitogen activated protein kinases (MAPK) used for?
used in mitosis and common in growth factor stimulation AMPLIFICATION - Reason it exists is because it allows for amplification, as first kinase may be present at really tiny conc which is amplified more for each kinase after so then the last MAPK can stimulate loads more proteins
69
what is the protein kinase cascade of MAPK?
MAPKKK --> MAPKK --> MAPK - shows how many phosphates - Each kinase activates the next via phosphorylation - allows signal amplification
70
what is a second messenger?
small intracellular molecules produced in response to receptor activation, they relay and amplify signals - in response to a transmitter - produced in response to hormones - Ca2+ is the most common
71
what is the point in the cAMP system?
PKA activation - diffusion of cAMP is rapid, occurs in seconds
72
what do phosphodiesterase (PDEs)?
break down cAMP to AMP
73
what receptor does the first messenger bind to?
a seven transmembrane receptor (crosses membrane 7 times), then goes to G-protein
74
what do G-proteins determine?
how long and strong a signal is
75
Physiology
flashcards
Decks in class (14)
# Cards
Brainscape helps you reach your goals faster, through stronger study habits.
© 2026 Bold Learning Solutions. Terms and Conditions