Neurotransmission Flashcards
Ion concentration gradients are established by proteins known as:
Active transporters - actively move ions into or out of cells against concentration gradient
Equilibrium potential
Equilibrium potential is the state in which the tendency of ions to flow across a cell membrane from regions of high concentrations is exactly balanced by the opposing potential difference (electric charge) across the membrane
For a given equilibrium potential ions will move in order to drive the membrane potential toward the equilibrium potential
Nernst Equation
Allows one to determine the equilibrium potential for an ion:
E (x) = RT/zF ln ([x]out/[x]in)
Ions are driven across the membrane:
At a rate proportional to the difference between the membrane potential & the equilibrium potential (driving force)
Goldman Hodgkin Katz
extended version of nernst equation taking into account relative permeability of ions –> used to calculate resting membrane potential
What is the capacitor, Resistor & battery in neuronal circuit:
Capacitor = Membrane of neuron: ability to store separate charge
Resistor (in series w battery)= Ion channels: when more ion channels are open - more ions able to flow: decreased resistance - increase in conductance
Battery = Transmembrane ion gradient: concentration gradient of a neuro is the external: internal ratio of ion concentration
What is the capacitor, Resistor & battery in neuronal circuit:
Capacitor = Membrane of neuron: ability to store separate charge
Resistor (in series w battery)= Ion channels: when more ion channels are open - more ions able to flow: decreased resistance - increase in conductance
Battery = Transmembrane ion gradient: concentration gradient of a neuro is the external: internal ratio of ion concentration
What is the capacitor, Resistor & battery in neuronal circuit:
Capacitor = Membrane of neuron: ability to store separate charge
Resistor (in series w battery)= Ion channels: when more ion channels are open - more ions able to flow: decreased resistance - increase in conductance
Battery = Transmembrane ion gradient: concentration gradient of a neuro is the external: internal ratio of ion concentration
Time constant:
The time it takes the membrane to reach 63% of its final voltage
*t = RXC
Property time constant is important for:
A) action potential conduction velocity
B) synaptic integration
the longer the time constant the longer the membrane will take to return to its resting membrane potential - implications for integration of multiple incoming signals
Property time constant is important for:
A) action potential conduction velocity
B) synaptic integration
the longer the time constant the longer the membrane will take to return to its resting membrane potential - implications for integration of multiple incoming signals
Membrane Voltage Changes that constitute an action potential
1) leak K+ channels open at rest - resting membrane potential slightly negative
2) Graded potential reaches threshold –> Depolarisation –> causes Na+ channels ope –> Na+ influx
3) Increase in membrane voltage, driven towards equilibrium voltage for Na+ (+62mv)
4) Inactivation gate closes - Na+ influx stops
5) K+ channels open –> K+ efflux
6) Membrane potential is driven towards potential for K+ (-80mv) - Repolarisation
&) V-gated K+ channels close but still overshoots - hyperpolarisation
Changes in ionic conductance:
Larger conductance for an ion (more channels open for that ion) - membrane potential driven towards equilibrium potential for that ion to a greater extent
V & Time dependent
Changing conductance:
a) amount of NT released
b) number of receptors
c) properties of receptors (phosphorylation)
Tetrodotoxin (TTX) blocks what channel
TTX blocks NA+ channels –> abolishes AP
Active vs Passive conduction
Active - voltage gated channels regenerate AP
Passive - No regeneration, follows electrochemical gradient
Length Constant
The measure of how far voltage travels before it decays
Low length constant –> voltage would decay over a short distance
Factors Affecting Conduction Velocity
- Large axon diameter –> speed up AP propagation
- Increases membrane resistance –> speed up AP propagation
- increases membrane capacitance –> slow down AP propagation
- Increased axial resistance–> slow down AP propagation
- Increased peak voltage-gated NA channel conductance –> speed up AP propagation
Increased Axial Resistance:
Increased axial resistance –> less cations are able to move along axon –> smaller length constant –> voltage travels over a smaller length therefore slower conductance velocity
How does myelin increase conduction velocity
Myelin reduces membrane capacitance - lower Cm = less cations tied up along inner surface of membrane = more cations available to depolarize other parts of membrane
Myelin increases membrane resistance - less cations leak out therefore more cation available to depolarise other parts of membrane
Saltatory Conduction - jumping between nodes
Synthesis of Peptides:
A) starts as pre-cursor peptide synthesized in the rough ER –> transported to Golgi apparatus (GA)
b) In GA: splits to yield active peptide
c) Buds from GA in a secretory vesicle containing the NT
d) Secretory vesicle transported down the axon & stored in the terminal ready for release
Synthesis of amino acids & amines:
a) precursor molecules are converted into NT by enzymes in the cytosol
b) when they leave the ER & GA - they travel along the axon to the terminal as as precursor molecule & remain in the cytosol
c) Then broken down into active NT by enzymes loaded into a vesicle
Stages of Synaptic Transmission *NB
1 - NT is synthesized & stored in vesicles
2 - An AP arrives at the presynaptic terminal
3 - Depolarization of presynaptic terminal - open of V-gated ca channels
4 - Influx of CA
5- Ca causes vesicles to fuse with presynaptic membrane (SNARE)
6 - Transmitter is released into synaptic cleft via exocytosis
7- transmitter binds to receptor molecules in postsynaptic membrane
8 - opening/closing of postsynaptic channels
9 - Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
10 - Retrieval of vesicular membrane from plasma membrane
SNARE proteins during NT Release:
SNARE proteins:
SNARE proteins have lipophilic end embedded in membrane & tail into cytosol
SNARE on presynaptic cell membrane = t-SNARE ; & on approaching vessicles = v-SNARE
Cytosolic end of SNARE bind tightly & dock the vesicle to the membrane
SNARE proteins alter conformation - lipid bilayer fuse, form a pore & NT released via exocytosis
NT release - Ca2+
V-gated Ca channels form part of active zone –> only respond when AP arrives
Internal [Ca] is low vs external [Ca] is high (4 fold) therefore large driving force for influx of Ca
Intracellular elevation of Ca is signal causes:
- Vesicle docking
- Vesicle fusion
- Vesicle NT release (exocytosis)
Proteins involved in vesicle structure
Dynamin & clathrin
