Neurophysiology and CNS Flashcards
diffusion
Movement of solute (ion) from area of high conc to low conc. Occurs through random thermal movement
facilitated diffusion
Required for ions - charged, not lipid soluble, cannot directly diffuse.
Ion channels (integral membrane proteins) create passage for molecules that cannot diffuse across membrane.
Resting membrane potential
-70mV
Function of Na+/K+ ATPase in RMP generation + maintenance
2 K+ in, 3 Na+ out
- RMP infl by both Na and K
- Large diffusion of K+ outwards (-90)
- Small diffusion of Na+ inwards (+60)
- No anion diffusion
- -70mV resting membrane potential
Depolarisation
Incr permeability to Na+ -> shifts membrane potential to E(Na)=60 -> Vm becomes more pos
Can be done by decr K permeability or change chemical gradient
* induces neuron firing
Hyperpolarisation
Incr permeability to K+ -> shifts membrane potential to E(K)=-90 -> Vm becomes more neg
Can be done by decr Na permeability or change chemical gradient
* inhibits neuron firing
Neuron
- Input from dendrites
- Soma or cell body
- Axon
- Output at axon terminal
Excitable cells
Harness diff in charge b/w outside and inside
- Have diff in ion concentration across a selectively permeable membrane
- More neg on inside
- Charge difference located at cell membrane
- Ex: neurons, cardiac+skeletal muscle
Electrical activity requires…
- Selectively permeable membrane
- Differential distr/charge gradient across membrane
Differential distribution
of ions greater on one side than other.
Neurons concentrate higher K+ inside, higher Na+ outside
K+ equilibrium potential
-90mV (potential from inside cell)
Na+ equilibrium potential
+60mV (potential from inside cell)
Relative ionic permeability
Greater an ion’s permeability, more influence on membrane voltage
Most cells: K+:Na+ = 50:1
K+ has much more influence; resting membrane potential (-70) is closer to -90 than +60
(Due to more open K+ channels at rest)
Action potential, regenerative event?
Electrical event triggered when Vm reaches threshold: rapid membrane depolarisation (goes toward ENa) -> rapid return toward RMP (-70)
Results from increased Na+ permeability, followed by incr K+ permeability
Regenerative event: AP in one part of membr initiates AP in further part of membr
Threshold
-50.
All-or-none
Stimuli below threshold: no AP.
Stimuli above threshold: AP of same size
Resting state
-70mV
- Na+ channel: activation closed, inactivation open. Na+ stays out
- K+ channel: activation closed. K+ stays in
Rising phase
-50 to ENa (+60). At peak, greater Na+ permeability from open Na+ channels
- Na+ channel: activation and inactivation open. Na+ flows in
- K+ channel: activation closed. K+ stays in
Overshoot
When Vm is above 0 during AP
Falling phase
- ENa to EK (-90)
- Na+ channel: activation open, inactivation closed. Na+ stays out
- K+ channel: activation open, K+ flows out
After-hyperpolarisation
- Vm is close to EK because K+ channels are open
- Rise back to RMP
- Na+ channel: activation and inactivation closed. Na+ stays out
- K+ channel: activation open. K+ flows out
voltage-gated ion channels
- Have voltage sensor which moves in response to d(Vm) -> coupled to activation gate (opens channel)
- Depolarisation -> opening of activation gate
- Most also have inactivation gate: depolarisation -> closes inactivation gate
- Na+ channel has both, K+ channel only activation
- At MRP: activation gate closed, inactivation gate open
Ionic conductance changes during AP
Na+ conductance (gNa) peaks in rising phase
K+ conductance (gK) peaks in falling phase
During afterhyperpolarization, gNa resting value, gK still elevated (K channels still open)
gK>gNa at rest (leaky K channels)
Absolute refractoriness
After AP, stimulus fails to evoke AP
- Some Na+ channels inactivated
- gK not at resting yet (voltage gated channels still open)
Relative refractory period
After AP, greater stimulus intensity is needed to generate AP
Generator potential
membrane depolarization occurring as a response to stimulus (initial depolarization sub threshold not considered part of AP).
Produced at sensory endings in periphery.
Stronger stimulus; larger depolarisation.
AP prod if GP->threshold
No refractory
Positive feedback depolarization
- Generator pot opens some Na+ channels
- Na+ conductance results in further depolarisation
- More depolarized -> activation gates open
- Keeps looping
Electrotonus
How electrical signals propagate
1. Current enters thru ion channel (Na+), depolarizing that region. (ATP needed)
2. + charge is adjacent to - charged membr regions; + charge propagates along. Depolarization spreads (passive process)
3. As current travels, charge leaks outward (electrotonic decay) - doesn’t propagate indefinitely
- Initial site was -40, adjacent keep decreasing until -70
4. Distance electrotonus can travel is length constant
Axons generally longer than length constant
Axial resistance
Depends on diameter. Ra incr when diameter decr
Length constant
lambda = sqrt(Rm/Ra)
propagation distance incr when:
- membrane resistance incr
- axial resistance decr/diameter incr
Active propagation
AP activates voltage-gated channels that regenerate depolarisation (let in Na+)
Resistance
Affects rate of AP propagation. diameter incr, resistance decr, AP faster
Capacitance
Affects rate of AP propagation
- +’s outside and -‘s inside are attracted to e/o. If there were a - outside, it would be repelled. Membrane is storing charge
- Changing charge takes time
- Proportional to surf area
- inversely proportional to membrane thickness
- myelin incr thickness: decr cepacitance
- Less capacitance -> charge changing faster -> faster AP propagation
myelin
- Incr AP propagation rate by decr capacitance
- Schwann cells in PNS
- Oligodendrocytes in CNS
- Allows voltage gated channels to be conc at nodes of ranvier
saltatory conduction
Between nodes of Ranvier:
- AP travels electrotonically
- myelin
- capacitance low, charge time short
- membrane thicker, Rm incr, longer length constant
At node of Ranvier:
- Active propagation
- Capacitance greater, charge time longer
- Slower AP
- Voltage gated channels
excitatory synaptic transmission
- Excitatory neurotransmitters (eg glutamate) bind to receptors that generate depolarizing PSPs
- brings Vm close to threshold
- Excitatory postsynaptic potential (EPSP)
- Receptor types: AMPA and NMDA receptor gated channels
AMPA-gated channel
On post-synaptic membrane, interacts w glutamate
- Allow both Na+ in and K+ ions out through pore
- Gen EPSP w potential around 0mV
- Brings postsynaptic neurons closer to threshold
- NMDA channels blocked by Mg2+
- Fast EPSP
Dendritic summation of EPSPs
- EPSPs decrease in amplitude while travelling to soma
- Single EPSP doesn’t reach threshold: summate to cause AP firing post-synaptically
- Temporal summation
Repetitive activation of single synapse, one right after the other. Reaches threshold at soma (insert pic)
- Spatial summation
Simultaneous activation of multiple synapses on same dendrite. Reaches threshold at soma (insert pic)
inhibitory synaptic transmission
Inh neurotransmitters (eg. GABA) bind to receptors which generate PSPs, Lowers Vm (away from threshold)
- Inhibitory postsynaptic potential (IPSP, below -70)
- GABAa receptor allows Cl- to enter; generates IPSP Ecl=-70
Synaptic transmission
- AP propagates in presynaptic neuron
- Ca2+ enters axon terminal (voltage gated Ca2+ channel)
- Neurotransmitter released thru exocytosis
- Neurotransmitter binds to postsynaptic receptor
- Specific ion channels open in postsynaptic membrane (chemical messenger gated ion channels)
Postsynaptic membrane effects
Binding of neurotransmitter induces conformational change of channel (opens)
- Ion movement generates synaptic current (Isyn)
- Isyn generates change in Vm (postsynaptic potential)
Motor unit
alpha motor neuron and all muscle fibers it innervates
- alpha motor neuron can branch many time; APs travel down all branches
- Simultaneously initiate excitation of each muscle fiber
- All motor units innervating skeletal muscle = motor unit pool
Anatomy of NMJs
- presynaptic terminal
- synaptic cleft
- postsynaptic membrane
- contacts muscle at midpoint
NMJ presynaptic terminal
- ACh synth and stored in vesicles
- Machinery for release of ACh: SNARE proteins and Ca2+ sensor associated w each vesicle and membrane
- Soma creates empty vesicles, transported on MTs
- Ach synth in terminal from acetyl CoA and choline
- Vesicles organized into active zones
NMJ synaptic cleft
- 50nm space
- basal lamina (ECM)
- Adhesion and alignment of active zones (pre) and muscle junctional folds (post)
- Acetylcholinesterase anchored in matrix, close to AChRs
NMJ postsynaptic membrane, perijunctional zone
- Longitudinal junction folds - SA for AChR
- AChRs at peaks of each fold - positioned opposite active zones
- Perijunctional zone: next to motor endplate, has many voltage-gated Na+ channels (site of AP initiation)
- second type of AChR in other areas of muscle membrane - fetal development, inflammation, denervation
Steps involved in neuromuscular transmission
- Each terminal end of a-MN simult activated by axonal AP
- AP activates voltage-gated Ca2+ channels, lets Ca2+ in
- ACh vesicles dock w synaptic membrane, exocytose ACh
- ACh diffuses across cleft, binds to AChRs at postjunctional folds
- AChRs open and allow Na+ in and K+ ions out = depolarization
- AChE in basal lamina hydrolyzes ACh into acetate and choline: terminates NM transmission
Postsynaptic junction physiology
- EPPs (end-plate potential) only propagates short distance
- Perijunctional region has many voltage-gated Na+ channels - ensures AP threshold reached
- EPP always large enough to reach AP threshold at perijunctional membrane (~40mV) (high safety factor - transmission and contraction always occur)
