Flashcards in deck_588494 Deck (33):
What is calcium responsible for or regulate?
FertilisationProliferationSecretionNeurotransmissionMetabolismLearning and memoryApoptosis and necrosis
Why do calcium levels have to be closely controlled?
Ca cannot be metabolised therefore have to move it in and out of the cytoplasm
What are the advantages and disadvantages to a steep Ca concentration gradient?
Advantages -- Increases in Ca concentration occurs rapidly with little Ca movementDisadvantages -- Ca overload leads to loss of regulation and cell death
What does the set up and maintenance of a Ca gradient rely on?
1. Impermeable membrane2. Ability to expel Ca across membrane using: --- Ca ATPase and Na-Ca exchanger3. Ca buffers4. Intracellular Ca stores --- rapidly and non rapidly releasable
How is the permeability of the membrane regulated?
Is regulated by the open or close state of ion channels
Describe the action of the Ca ATPase
Moves Ca out at the expense of ATP so against a chemical. And concentration gradient
Describe the feedback mechanism for Ca ATPase What characteristic for affinity and capacity does it have?
An increase in [Ca] occurs and Ca binds to calmodulin (trigger protein) The Ca-calmodulin complex binds to Ca-ATPase The Ca-ATPase removes Ca from the cell -- high affinity and low capacity
Describe the action of the Na/Ca exchanger. What capacity and affinity does the channel have?
[Na] is into the cell, so it is used as the driving force using a Na-K-ATPase Antiporter is electrogenic so it removes calcium best at a resting potential Allows for Ca to be removed against its concentration gradientLow affinity with a high capacity (Good at high concentrations)
What do calcium buffers do?
Limits calcium diffusion in the cell-- independently regulates the movement of ions
What are the effects of calcium buffers?Name some Ca buffersWhat happens when there is an incresed saturation for the buffers?How far can a Ca ion normally diffuse before it encounters a buffer molecule?
Ca diffuses more slowly. Calreticulin, calbindin and calsequestrin Ca can diffuse further in the cell because it is not limited by the bufferNormal amount of diffusion to reach a binding molecule is 0.1 -0.5 micrometres
How is the [Ca] elevated then returned to normal levels?
1. Ca influx across the membrane through specific channels--- voltage gated channels and receptor-operated ion channels2. Ca is released from rapidly releasable stores --- G-protein coupled receptors and calcium induce Ca release3. Non-rapidly releasable stores
Describe the two ways that Ca influx occurs across a plasma membrane
Voltage operated Ca channels-- senses depolarisation which opens an aqueous pore to allow Ca into the cellIonotropic receptors (receptor-operated ion channels)-- e.g. NMDA receptors for glutamate and nicotinic ACh receptors
What facilitates the relates of Ca from rapidly releasable stores?How does in it get Ca into the store?What is the concentration of Ca inside the stores?
SERCA pump -- sarcoplasmic/endoplasmic reticulum Ca2+ ATPase Uses ATP to bring Ca in against its steep gradient. The Ca binds to calsequestrin. The release of Ca is controlled by release channels. Concentration = 1mM
What are the two ways that the release of Ca from intracellular stores is controlled?
1. G-protein coupled receptors 2. Calcium induced calcium release
Describe the process of calcium release via G-protein receptorsWhere are G-protein receptors found?What proportion of drugs target these receptors?
Molecule binds to receptor which interacts with a G-protein which mediate the release of effector molecules inside the cell. Majority of cells contain G-protein receptors30-50% of drugs target these receptors
What molecules can stimulate GPCR mediated signalling?How are G-proteins activated?
Hormones, neurotransmitters, ions, odourants, taste Are heterotrimeric proteins which splits into subunits when it is activated
What subunits does a heterotrimeric g-protein split into?
Alpha subunit either affects phospholipase C or adenylyl cyclase-- Alpha(q) affects phospholipase C which produces IP3 and diacylglycerol-- Alpha(s) and (i) are effectors of adenylyl cyclase, which generates cAMP (secondary messenger) which activates protein kinase A Beta subunit with gamma subunit affects ions channels
What does g-protein alpha(q) do?
Breaks down PIP2, a component of membrane phospholipid -- this releases IP3 which stimulates IP3 receptors on SR/ER -- induces release of intracellular stores of Ca E.g. Muscarinic M3 receptor in smooth muscle of airways --> contraction of bronchioles
How does calcium induced calcium release occur?Give a characteristic of ryanodine receptors.
Calcium influx into a cell will bind to ryanodine receptors on the surface of SR/ER.This causes Ca to be released from the SR/ER Ryanodine receptors are not endogenous to humans -- are a plant alkaloid
Where are ryanodine receptors commonly found?Where are they located in the cell?What does the release of Ca around the contractile proteins allow for?
Cardiac myocytesNear to membranes A strong coordinated contractile event
Describe the process of depolarisation in cardiac myocytes
Depolarisation occurs along the cardiac myocytes which causes Na channels to open, allowing Na to move from t-tubules into the cell. The Na influx causes Voltage gated Ca channels to open. The influx of Ca binds to ryanodine receptors, causing Ca to be released from the ER. Increased [Ca] causes heart contraction.
What percentage of the contraction process is stimulated by the influx and the intracellular store?
85% from intracellular stores15% from calcium influx
How is calcium removed from the cell after depolarisation?
MINOR ROUTE FOR REMOVALThe Na/Ca exchanger will favour the outflow of calcium when repolarisation starts, in order to lower the high [Ca] from the cell. MAJOR ROUTE FOR REMOVALThe SERCA pump will pump calcium back into the ER/SR to prepared for another release event.
What allows for the prolongation of polarisation in cardiac cells?
1. Ca channels show slower activation and inactivation the Na channels2. Low K conductance at depolarised potentials
How does calcium control skeletal muscle contraction?
Calcium binds to troponin which undergoes a conformational change, which moves tropomyosin to reveal the actin binding sites for myosin head groups.
What occurs in skeletal muscle in the presence of ATP?
Myosin undergoes cycles of attachment and detachment alongside the movement of myosin head groups, causes the sliding of actin along myosin bundles to contract the myocyte.
Where are non-rapidly releasable stores of calcium held?What type of signalling do they take part in and why?
In the mitochondria Normal Ca signalling due to micro domains -- they sense high levels of Ca as they are close to Ca channels.
How do the mitochondria take up calcium?Give some characteristics of the channels.
Using energy from the respiratory chain proton production -- are uniporters-- low affinity but high capacity
What are the roles of mitochondrial calcium uptake?
1. Regulate calcium buffering2. Regulate the pattern and extent of Ca signalling3. Stimulate mitochondrial metabolism -- matches demand and energy supply4. Has a role in apoptosic cell death -- due to altered redox potential
Wy must calcium levels be restored to a cell quickly?How does it do this?
Allows muscle cells to relax Stops the release of excess neurotransmitter Cells use transient signals -- levels only increase for a sort period of time
How does the [Ca] return to normal?
Signal is terminatedCalcium is removedCalcium stores are refilled
How are calcium stores refilled?
1. Recycling of released cytosolic Ca (in cardiac myocytes)2. Capacitative Ca entry -- ER sends out a depleted signal in order to refill the Ca stores which are preferentially used