Ca signalling Flashcards
What are the components of the calcium toolkit?
On - cause calcium levels to be elevated through an influx of transporters or a release from stores
Off - depleting stores down to normal levels through buffers, pumps and transporters
How does Ca carry out a diverse number of functions?
Small differences in spatial and temporal resolution
What is the state of Ca at resting state?
- arounf 100nM concentration
- inhibitory function on gene transcription and neurite extension
What are the sources of Ca?
- ER
- Mitochondria
- Acidic vesicles (lysosome - can cross talk with ER for larger Ca release)
- High levels of extracellular Ca allow for influx when required
What is the main Ca receptor?
Ryanidine: 3 isoforms
Which Ryanidine receptor is in the skeletal muscle?
Type 1: activated by mechanical coupling. Change in membrane potential activates Ca channel and dyhropyridine receptor. The latter change causes conformational difference allowing it to interact with RyR1 allowing Ca2+ to enter
Which RyR is found in the heart?
Type 2 - Ca enters through v gated channels and then binds to this channel causing Ca mediated Ca release from stores
How do IP3 receptors mediate Ca release?
Hormone activates G coupled receptor which activates PLC, which breaks PIP2 into DAG and IP3. IP3 then binds to RyR receptor to release Ca
Describe store-operated Ca entry
ER has a STIM receptor, which has EF hands capable of sensing Ca levels. When low these can oligomerise to form a couple and coplex with ORAI1 at the plasma membrane channel. Through the ion channel TRIPC can allow Ca influx into the store
What are the ‘on’ mechanisms of the Ca toolkit?
- SOCE mechanism
- Voltage operated Ca channels due to an electrochemical gradient
- Release from intracellular sores through IP3 aided by RyR
- Sensors of Ca changes e.g Troponin C alters conformation to allow actin and myosin to slide over eachother
What are the ‘off’ mechanisms of the Ca toolkit?
- Buffers such as the mitochondira which contains calbindin proteins (parvalbumin)
- Pumps and exchanges
- Pumps on ER may pump Ca back into stores to be recycled
(note: pumps against concentration require ATP)
What are the different time domains Ca may act on?
Exocytosis - ms
Contraction - s
Transcription - min
Fertilization - days
Give an example of an effect on Ca frequency and amplitude
- Hystidine binds to G-coupled receptors and activates IP3, at high concentration causes a high frequency and amplitude of Ca response
- In weaker response there is recruitment of less receptors on membrane and stores, therefore less release and less response
Give an example of all the members of the toolkit for the cardiac myocite
stimulus - membrane depolarisation
Transducers - voltage gated Ca channels
Channels - bind to RyR/IP3R which if sufficient, binds to troponin C causing contraction
Pumps - Sarcoplasma Ca ATPase (SERCA) pumps Ca back into ER stores, calcuquestrin in ER binds up to 50 Ca to decrease gradient
Pumps - Ca/Na exchange and K/Na pump to avoid AP
What happens in heart arrhythmia?
K/Na exchange is downregulated causing early afterhyperpolarisation which results in more Ca release, therefore less is available for the next contraction which is then weaker
