Session 5 Flashcards
(16 cards)
Describe the role of Ca2+ in neurotransmitter release at the nerve terminal
Depolarisation opens voltage gated Ca2+ channels Ca2+ binds to synaptotagmin Vesicle brought close to the membrane Snare complex makes a fusion pore Transmitter released through this pore
Name a blocker of an L-type Ca2+ channel
Dihydropyridines
How does 2*ACh binding to nAChR on the post junctional membrane produce an action potential?
Produces an end plate potential, raising the membrane to potential which then fires an AP
Describe the action of tubocurarine
Competitive blocker at the recognition site for ACh on nAChR.
Describe the action of succinylcholine
It is a depolarising blocker of the nAChR. It causes sustained depolarisation so adjacent Na+ channels are not activated because of accommodation.
What is myasthenia gravis?
An autoimmune disease targeting nAChR. Patients suffer profound weakness which increases during exercise and fatigue. Caused by antibodies directed against nAChR on post synaptic membrane of skeletal muscle. End plate potentials are reduced in amplitude.
Each quantum of ACh release produces a smaller response than normal. Treated with ACh esterase inhibitors.
What cellular processes are calcium sensitive?
Fertilisation, secretion, neurotransmission, metabolism, contraction, apoptosis and necrosis.
What are the advantages and disadvantages of a large inward Ca2+ gradient?
+ changes in intracellular Ca2+ occur rapidly with little movement of ions
+ little Ca2+ has to be removed to establish resting conditions
- energy expensive
- inability to deal with Ca2+ easily leads to a loss of regulation and cell death
What does the Ca2+ gradient rely on?
Relative Impermeability of plasma membrane
Expulsion of Ca2+ across the plasma membrane
Ca2+ buffers
Intracellular Ca2+ stores - both rapidly and non-rapidly releasable.
How is Ca2+ expelled across the plasma membrane?
Ca2+ ATPase (PMCA): high affinity, low capacity. Ca2+ binds to calmodulin. Ca2+-calmodulin bonds to PMCA, removing Ca2+.
Na+/Ca2+ exchanger (NCX): lower affinity, higher capacity. Na+ gradient used as driving force. Transports 3Na+ into the cell for every Ca2+ out. Electrogenic - works best at resting membrane potential.
How do Ca2+ buffers help maintain the Ca2+ gradient?
They limit diffusion - ATP and Ca2+ binding proteins such as parvalbumin, calhindin, calreticulin and calsequestrin. Diffusion depends on the concentration of binding proteins and their level of saturation.
What methods increase intracellular concentrations of Ca2+?
Ca2+ influx across plasma membrane (altered permeability)
Ca2+ release from rapidly releasable stores
Ca2+ release from non-rapidly releasable stores
How may Ca2+ enter across the plasma membrane?
Voltage operated Ca2+ channels (VOCC) - triggered by depolarisation
Ionotropic receptors - ligand gated
How is Ca2+ released from rapidly-releasable intracellular stores?
Sarcoendoplasmic reticulum can store large quantities of Ca2+ by binding to proteins such a calsequestrin. SERCA allows active uptake of Ca2+. Rapid release by either:
- IP3 receptors - IP3 released via activation of GPCRs which causes Ca2+ to be released by acting on IP3 receptors on the ER membrane
- ryanodine receptors - Ca2+ that enters the cell through VOCCs acts on these receptors on the ER membrane causing calcium induced calcium release. Ensures strong and coordinated contraction in cardiac myocytes.
How is Ca/+ released from non rapidly releasable stores?
Ca2+ is taken into mitochondria when intracellular Ca2+ is dangerously high. Mitochondria also participate in normal Ca2+ signalling due to microdomains - areas of cytoplasm with a higher concentration of Ca2+ due to their proximity to a channel.
Mitochondrial uptake is important for Ca2+ buffering, stimulation of mitochondrial metabolism and role in apoptosis.
How is intracellular Ca2+ returned to basal levels?
Termination of signal - desensitisation/ligand removal
Ca2+ removal
Ca2+ store refilling - by recycling of released Ca2+ or through capacitative store operated channels (SOC).
