Describe the transmitter release pathway.
- Ca2+ enters through voltage gated calcium channels.
- Ca2+ binds to SYNAPTOTAGMIN on a vesicle and brings the vesicle to the plasma membrane.
- These band to a SNARE COMPLEX to form a FUSION PORE.
- Neurotransmitter released.
What are the advantages and disadvantages of a large inward gradient for Ca2+?
The inward calcium gradient [Ca2+] is 1-2mM to 100nM.
ADVANTAGES Little movements in Ca2+ cause large changes in [Ca2+]i so Ca2+ is used to regulate many processes e.g. - Fertilisation - Proliferation - Secretion
DISADVANTAGES
Ca2+ overload leads to cell death due to loss of regulation.
Give the FOUR ways that the Ca2+ gradient is SET and MAINTAINED?
- MEMBRANE IMPERMEABILITY (channels usually closed)
- EXPULSION
a) Plasma Membrane Ca2+ ATPase (1Ca out: 1H in)
- requires CALMODULIN to bring Ca2+
b) Na+ Ca2+ Exchanger (1 Ca out: 3Na in) - Ca2+ BUFFERS (ATP and Ca2+ binding proteins)
- slow Ca2+ diffusion this reduces its effects across the cell
- TRIGGER PROTEINS also bind Ca2+ to alter their function - INTRACELLULAR STORES
a) Rapidly releasable (ER or SR)
b) Non Rapidly releasable (Mitochondria)
What are Microdomains?
Microdomains are regions where Ca2+ concentration is in excess of the rest of the cell such as around an open Ca2+ channel.
Give the THREE ways intracellular calcium concentration is altered.
- INFLUX across plasma membrane
a) Voltage Operated Ca2+ Channels
b) Receptor Operated Ca2+ Channels (e.g. glutamate receptors) - RAPIDLY RELEASABLE STORES (ER or SR)
- SERCA imports Ca2+
- Calsequestrin binds Ca2+ in SR
- Ca2+ leaves SR via release channels - NON RAPIDLY RELEASABLE STORES (mitochondria)
- Uniporter imports Ca2+
What are the FOUR functions of mitochondrial Ca2+ buffering?
- Ca2+ buffering is a PROTECTIIVE mechanism occurring when Ca2+ concentrations are too high.
- The Ca2+ stimulates METABOLISM in mitochondria.
- Ca2+ is also involved in SIGNALLING at microdomains.
- The mitochondria are involved in APOPTOSIS as they release their stored Ca2+
What are the advantages and disadvantages of a large inward gradient for Ca2+?
The inward calcium gradient [Ca2+] is 1-2mM to 100nM.
ADVANTAGES Little movements in Ca2+ cause large changes in [Ca2+]i so Ca2+ is used to regulate many processes e.g. - Fertilisation - Proliferation - Secretion
DISADVANTAGES
Ca2+ overload leads to cell death due to loss of regulation.
Give the FOUR ways that the Ca2+ gradient is SET and MAINTAINED?
- MEMBRANE IMPERMEABILITY (channels usually closed)
- EXPULSION
a) Plasma Membrane Ca2+ ATPase (1Ca out: 1H in)
- requires CALMODULIN to bring Ca2+
b) Na+ Ca2+ Exchanger (1 Ca out: 3Na in) - Ca2+ BUFFERS (ATP and Ca2+ binding proteins)
- slow Ca2+ diffusion this reduces its effects across the cell
- TRIGGER PROTEINS also bind Ca2+ to alter their function - INTRACELLULAR STORES
a) Rapidly releasable (ER or SR)
b) Non Rapidly releasable (Mitochondria)
What are Microdomains?
Microdomains are regions where Ca2+ concentration is in excess of the rest of the cell such as around an open Ca2+ channel.
Give the THREE ways intracellular calcium concentration is altered.
- INFLUX across plasma membrane
a) Voltage Operated Ca2+ Channels
b) Receptor Operated Ca2+ Channels (e.g. glutamate receptors) - RAPIDLY RELEASABLE STORES (ER or SR)
- SERCA imports Ca2+
- Calsequestrin binds Ca2+ in SR
- Ca2+ leaves SR via release channels - NON RAPIDLY RELEASABLE STORES (mitochondria)
- Uniporter imports Ca2+
What are the FOUR functions of mitochondrial Ca2+ buffering?
- Ca2+ buffering is a PROTECTIIVE mechanism occurring when Ca2+ concentrations are too high.
- The Ca2+ stimulates METABOLISM in mitochondria.
- Ca2+ is also involved in SIGNALLING at microdomains.
- The mitochondria are involved in APOPTOSIS as they release their stored Ca2+
Give THREE forms of calcium release channels on the SR and how each works.
- IP3 RECEPTOR (responds to IP3 once a Gaq GPCR is activated)
- Ryanodine 2 Receptor - CALCIUM INDUCED CALCIUM RELEASE
- Ryanodine 1 Receptor - CONFORMATIONAL COUPLING with VOCC (i.e. forms connection between SR and transverse tubule)
Which THREE transporters or channels cause the rise in cytosolic Ca2+ which induces contraction of cardiac myocytes?
- VOLTAGE OPERATED Ca2+ CHANNELS
(open in response to depolarisation and allow a small amount of Ca2+ to enter from the ECM) - RYANODINE 2 RECEPTORS
(Calcium induced calcium release - some Ca2+ from VOCCs bind causing massive release of Ca2+ from SR)
3. Na+ Ca2+ EXCHANGER (Reversed) (Depolarisation causes NCX reversal leading to more Ca2+ influx) Although reverts to normal when: a) Repolarisation is underway b) Ca2+ concentration increases
Ca2+ is toxic if it remains high for too long therefore the basal state must be restored. What THREE ways is this done by?
- TERMINATION of signal
- REMOVAL of Ca2+ from the cell (via PMCA and NCX)
- STORE REFILLING
What is capacitative Ca2+ entry?
CAPACITATIVE CHANNELS in the plasma membrane (or store operated Ca2+ entry channels) are activated when Ca2+ is depleted from the stores.
This results in intake if Ca2+ from outside of the cell and SERCA pumps it into the SR.
