Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
19 Cards in this Set
- Front
- Back
|
Second Messenger
|
•Themost ‘direct’ messengers are usually ions, e.g. Na+, entering via the ligand gated Achreceptor – to change membrane potential.
•Calciumions (Ca2+) – play a role in most cells •Lipidderived second messengers are from membrane phospholipids, e.g. IP3, DAG, ceramide. •Cyclicnucleotides are another class of second messengers – cAMP,cGMP. |
|
|
Secondmessengers: cAMP and Calcium ions
|
- Themost ‘common’ and best characterised
- Theygreatly amplify the cell surface ‘signal’, - Recruit the actions of manyintracellular proteins - ‘Construct’ the temporal (time dependent, i.e. earlyand delayed or prolonged) response scenarios. |
|
|
Examples of Calciumas a Signalling Ion
|
•In ova, fertilisation triggers a Ca2+ wave that initiates development.
•In muscle cells increased intracellularCa2+ causes contraction. •In secretory cells including neuronsincreased intracellular Ca2+ triggers secretion. |
|
|
Ca2+ makes an effective signal because...
|
Intra-cellular levels are low (10-7M) and extra-cellular levels (and thosein intracellular stores) are high (10-3M).
|
|
|
What are the two main ways intracellular[Ca2+] is kept low?
|
- Extrusion
- Sequestration |
|
|
Extrusion
|
- The Ca2+ - ATPasepumps via the plasma membrane with a rate of 30 ions per second (high affinityfor calcium).
- 1 Ca2+ leaves whereas 2H+ enters. Totalenergy used for this exchange is 1ATP. - Na+ - Ca2+ exchanger (with a rate of 2000 Ca2+per a second). - 1 Ca2+ leaves and 3 Na+ enters, or, 1 Ca2+and 1 K+ leaves and 4Na+ enters. |
|
|
Sequestration
|
- Utilises the Ca2+ - ATPase pump onthe sarcoplasmic/endoplasmic reticulum.
- The mitochondria acts as a ‘sink’ athigh intracellular Ca2+. - When calcium needs to be shifted from the cytosol into theintracellular stores. - Calcium can be stored in the endoplasmicreticulum/sarcoplasmic reticulum with the use of the pump. - Otherwise, calciumions can traverse the outer mitochondrial membrane via simple diffusion down aproton gradient |
|
|
Calciumbinding proteins
|
- Buffers the intracellular calcium concentration.
- The cytosol contains many proteins thatsequester Ca 2+ ,parvalbumin, calbindin-D28K, calreticulin, sequestrin, calmodulin. - Calcium is essential for life and has arole as a unique signalling ion in most cells of the body. - The skeleton is a store of Ca2+ to buffer cells and thecirculation from any lack of Ca 2+ |
|
|
Example of processes using calcium signalling
|
•Fertilisation
•Development. •Differentiation •Adhesion. •Growth. •Cell division. •Movement. •Contraction. •Exocytoticsecretion |
|
|
Howis Intracellular [Ca2+] Raised?
|
•Influxof Ca2+ from the extracellular space
•Releaseof Ca2+ from intracellular storage organelles: –Smoothendoplasmic reticulum. –Sarcoplasmicreticulum (muscle cells). –Mitochondrion. •Manycells use a combination of both methods |
|
|
Influxof extracellular Calcium.
|
•Thecell membrane is almost impermeable to Ca2+.
•ThereforeCa2+ entry relies exclusively on the threetypes of Ca2+ channels. –Voltagesensitive –Receptor-activated –Stretch-activated |
|
|
Voltagesensitive Ca2+ channels
|
•Sensitiveto changes in membrane potential
•Openedby membrane depolarisation –Open/closedstate determined by membrane potential. - Allthese channels are blocked by cadmium (Cd2+) |
|
|
Receptor– Activated Channels
|
– Opened by a ligand(neurotransmitter, hormone etc.) binding to a receptor
– May be directly activated(ligand-gated channel) or coupled by G-protein or second messenger. (e.g. b-adrenoceptor) |
|
|
Stretch-activatedchannels
|
– Openedby stretching of cell membrane.
– Maybe cationnon-specific and work via MP – Predominantlyon muscle and endothelial cells |
|
|
Releaseof Intracellular Ca2+
|
–Ca2+ inthe SR/ER is stored bound to calsequestrin.
–Ca2+ inthe SR/ER store can be released by IP3. –Ca2+ canalso stimulate its own release (Ca2+-induced-Ca2+-releaseor CICR) through a Ca2+sensitive ryanodine receptor on the SR. –Canalso be released by changes in membrane potential. |
|
|
Muscarinicreceptor activation & intracellular Ca release.
|
- Ryanodinereceptors are most commonly found inmuscle, of all types.
- They are activated when intracellular[Ca] rises above a certain ‘trigger’ level, and close when [Ca] is high |
|
|
StoreOperated Ca2+ entry
|
•Whenthe intracellular Ca2+store is emptied, it signals to theplasma membrane to allow Ca2+ entry from the extracellular space.
–STIM/Orai1 channels |
|
|
Mediationof Ca2+ Signals
|
•Theeffects of Ca2+ are mediated by Ca2+ binding proteins.
– Calmodulin(CaM)is expressed in all cells. – TroponinC is used by skeletal and cardiac muscle. – TheCa-calmodulincomplex targets a variety of cellular proteins to stimulate or inhibit theiractivity.(PKI, MLCK, NO synthase, Protein Phosphatases, ion channels). |
|
|
Wheredo second messengers signal?
|
•Justas the membrane is not a homogeneous structure – neither is the cell interior.
•Cellsare compartmentalised •Secondmessengers have domains of action •Ca2+ ions for example produce different cellresponses through ‘global’ or ‘focal’ changes in [Ca2+]. |
