Unit 1 - Basic properties of NS Flashcards
Ways for Na+ and K+ to cross neuron membrane
- proton pumps - low turnover rate
2. ion channels - high turnover rate (more effective!)
Major properties of Ion Channels
- Gated! (voltage, ligand, or mechanical/stress-gated)
- selective permeability
- voltage-gated: K+, Na+, Ca+
- ligand-gated: cation (K+, Na+…Ca2+) OR anion (Cl-) selective - HIGH flux rates! (efficient in transporting ions)
type 1 episodic ataxia
loss of muscle coordination due to a genetic disorder of ion channel(s)
–> mutation in voltage-gated K+ channels
Type 2 episodic ataxia
loss of muscle control due to genetic disorder of ion channels
–> point mutations in voltage-gated Ca2+ channels
= exercise induced
voltage-gated Na+ channel mutations
change function of ion channels –> affect pain sensation
- most mutations in Nav1.7 –> hyperexcitability (excessive pain sensation)
- nonsense mutations in Nav1.7 –> NO pain sensation
structure of voltage-gated Na+ channels
4 repeats, each with 6 membrane-spanning domains.
BUT only 1 protein forms the whole channel (encoded by 1 gene)
- H5 (aka P region) = pore-forming portion
- S4 domain = voltage gating portion
(conf. change to shift + charge –> open channel)
Criteria for Neurotransmitters (NTs)
- synthesized in neuron
- Stored in presynaptic nerve terminal
- Mechanism for release (tied to stimulation, usually Ca2+ dependent)
- mechanism for degradation (in synapse)
Vesicular transporters
on presynaptic vesicles, swap transmitter for H+ 4 types (for ACh, Gaba, glutamate, amines)
Mechanism of Small molecule NT synthesis
(Ach, NE, Gaba, etc.)
- synthesize enzymes in soma;
- transport enzymes to presynaptic terminal
- synthesis and packaging of NTs IN presynaptic terminal
- -> release of NT (synthesis and release of these is FAST!)
Lambert-Eaton Myasthenic Syndrome
Autoimmune attack on pre-synaptic calcium channels, decreases the # quanta released at NMJ.
- -> muscle weakness, reduced tendon reflexes, ANS dysfunction
- associated w/ small cell lung carcinoma
Major parts of a neuron
- dendrite (receives signals, no myelin –> signals degrade towards soma)
- soma (cell body, w/ all cell machinery, ER, nucleus, etc.) aka: perikaryon
- Axon (sends signals to next target - ie: neuron or muscle)
Axon Hillock
junction btwn soma and axon, where the AP is initiated in axon.
- -> “center of electrical excitement”
- w/ high amt Na+ channels*
2 types of glial cells
= supporting cells for neurons, 10x # neurons!
- oligodendrocyte - in CNS
- Schwann cell - in PNS,
Golgi stain used for?
Golgi stain –> dendrites appear black.
- allows study of structure of dendrites in tissue
ie: pyramidal in cortex
Motor axons synapse on…?
Motor end plate!
motor axons don’t actually synapse directly on muscle
convergence
Any one neuron can receive many different axonal projections
divergence
Any one neuron can send axonal projections to many targets (ie: other neurons)
spines
= small projections off dendrites (look like tree buds),
w/ NTs and ion channels
–> expand signal receiving area of the dendrite
speed of signal transduction depends on…
- diameter of the axon – INcrease speed
(0.2 - 20 m^-6 –> 120-235 m/s) - resistance
- myelination –> INcrease speed
(external resistance)
molecular transport along axon
- uses microtubules as highways for molecular transport to either end of axon.
- anterograde: from soma to pre-synaptic terminal
(NTs - whole or parts, vesicles, proteins, lipids) - retrograde: from pre-synaptic terminal to soma (GF, rabies virus)
speed of molecular transport along axons
- organelles/molecs: ~400mm/day
- cell structures: SLOW. 0.2 mm/month
- -> neurons grow VERY slowly! (hard to regrow when damaged)
Parts of CNS
- Brain
- Spinal cord
- -> collection of cell bodies = “nucleus”
parts of PNS
- Cranial nerves (CNI-XII)
- spinal nerves (motor and sensory)
- cervical (8), thoracic (12), lumbar (5), sacral (6), coccygeal.
- -> collection of cell bodies = “ganglion”
- cervical (8), thoracic (12), lumbar (5), sacral (6), coccygeal.
White matter
neural tissue rich in myelinated axons
gray matter
neural tissue consisting mostly of cell bodies (soma)
decussate
when a nerve/neural tract crosses the midline
ie: opti chiasm
Na+/K+ ATPase
Active ion transporter, powered by ATP hydrolysis;
establishes K+/Na+ gradient.
* LOW rate of turnover –> 10^3 cycles/sec.
–> not fast enough to cause depolarization or hyperpolarization
Ion channels for Neural signaling
* used to QUICKLY change membrane potential for AP, HIGH flux (turnover rate): ~10^7 - voltage-gated (Ca++, Na+, K+) - ligand-gated (K+, Na+, Cl-) - mechanical
rectification
When make the inside of a neuron positive, the cation channel will open; if make negative, the channel will stay closed.
TEA (tetraethylammonium)
toxin that blocks delayed rectifier K+ channels
- sometimes used in voltage clamping to isolate specific channels
K+ leakage channel
(aka: TASK-1 channel) = open at resting potential, helps w/... - generate resting potential - falling phase of AP.
Voltage-gated Na+ channel
4 repeats of 1 protein, similar activation curve to volt-gated K+ channel, BUT…
- Faster activation
- self-INactivating (ball and chain model)
- must hyperpolarize before second depolarization
- Blocked by TTX (tetrodotoxin) and STX (Saxotoxin, in red tide)
Voltage-gated Ca+ channel
= 1 continuous protein (similar to Na+ channel); But: longer C terminal, w/ more bindings.
L-type - high volt. activated. in skeletal mm and neurons;
- sensitive to dihydropurines
N-type - High volt. activated, in pre-synaptic terminals
T-type - LOW voltage activated **all types have varied inact. time
Functions of Ca+ in neurons
- Release of vesicles from pre-synaptic terminals
- muscle contraction
Internal [Ca++]…
- modulates other ion channels - Enzyme activation
- process outgrowth and synaptic plasticity - gene expression
Patch Clamp
= test for a SINGLE ion channel, measures channel conductance.
- conductance is constant (= 1/resistance)
- transition btwn open and closed is instantaneous
Resting Potential
the potential of a neuron at rest (not firing); primarily reflects Ek.
- net charge across membrane MUST be neutral
- maintained by Na+/K+ ATPase
- deviates from Ek at very LOW [K+]!
- different than equilibrium potentials (when 1+ ion in permeable)
Electrochemical Equilibrium Potential
the voltage at which a) and b) balance each other out.
a) flux due to chemical gradient
b) flux due to voltage (charge) gradient
* measured for single ions (Ek, Ena), also for net membrane (Em)
Nernst potential
Calculates the Electrochemical Equilibrium value for a given ion.
Eion = V= (58/z)*log([ion]out/[ion]in)
* z= charge of ion (ie: Ca = +2, Cl = -1)
GHK Equation (Goldman-Hodgkin-Katz)
Calculates membrane electrochemical equilibrium (Em),
takes into account all permeable ions.
Em = (58/z)log((Pk[K]o + Pna[Na]o + Pcl[Cl]i)/(Pk[K]i + Pna[Na]i + Pcl[Cl]o))
* P = relative ion permeability –> Pk usually»_space; Pna
Characteristics of Action Potential
- All-or-Nothing / must meet threshold to get AP
- Rapid, no decrement
- rising and falling phases
- positive feedback (some depolarization makes more reaching threshold easier)
Generation of an Action Potential
- (resting) K+ leakage channels maintain Em
- (rising) open Na+ channels –> depolarize {Na+ INTO cell}
- (falling) Na+ channels INactivate, close;
K+ rectifier channels open, {K+ into cell, Na+ out of cell}
K+ leakage channels open –> re-and hyper-polarize
