B1W2: Physio Flashcards
Assumptions of Action potential
- AP does not decrease in amplitude as it propagates
- AP occurs duet o decrease in transmembrane resistance i.e. increase in conductance/ion permeabilities
- Cooling axon slows AP and widens it
- Reducing [Na]o decreases amplitude, magnitude of pos. overshoot and velocity (sodium hypothesis bc makes GHK more neg.)
What amount of Na+ is needed to make an AP?
VERY SMALL AMOUNT
Exception: large diameter axons
Signifigant increase in [Na+] and decrease in [K+]
Will screw up ATP Na+/K+ pump if it isn’t already blocked by ischemia/hypoxia
Constant stimulation
Voltage clamp on action potential
Measures specific currents at Vm
- no ionic current at hyperpolarization (-140 mV)
- at depolarized (-20 mv), positive current inward followed by outward
Tetrodoxin
TTX, blocks Na+ channels
Leads o respiratory paralysis and death
Dihydropyridines
Block Ca2+ channels
TEA
tetraethylammonium
Blocks K+ channels
What happens if you clamp Vm at the E of an ion?
Current=0
What happens if you clamp Vm at more pos. than -30mv?
Inward current starts to lessen
After the ENa, Na+ will go in opposite direction!
Equation for current of ion w/ voltage clamp
i of ion=g(ion) x (Eion-Eclamp)
Channel activations
- action potential initiated
- causes Vm to more positive level by opening voltage-gated channels
- gNa and gK up, but gNa faster so its peak occurs sooner
- Reaches threshold, Vm at which iNa=iK
Electrical excitability
Ease of firing AP
Proportional to 1/(Vth - Vm)
Want to increase excitability by making Vth more neg. or Vm more pos.
Need to decrease (Vth-Vm)
Incease in [Ca2+] o and excitability
Moves Vm towards +
Decreases excitability because Ca2+ binding to membrane proteins, more pos. charge need to be removed to depolarize
Decrease in [Ca2+]o and excitability
Increases excitability by decreasing current of Ca2+
[K]+ o increase affect on excitability
moves Vm towards Vth, up excitability
Current of K+ out of cell is down so Vm stays more +
Properties of ion channels
Selective (due to specific amino acids)
Inactivation/activation controlled
S4 voltage-gated protein domain
Lysine and arginine positive residues
Senses voltages
S5-S6 voltage-gated channels
Pore region
Has amino acids that recognize substrate
Activation of ion channels in Na+
S4 helices attrached to inside membrane usually
Depolarization causes helix to be attracted to extracellular side, opening pore
Inactivation/closing of ion channels
In Na+: hinged lid
In K+: ball and chain, amino acids near NH3+ work
Channels can only be reactivated by going back to resting state
Depolarization blockade
Can’t initiate AP because Na+ channels remain in inactive state due to depolarization
Na+ channels remain inactivated because S4 still has AP charges on it
Ways to initiate depolarization blockade
Increase in neurotransmitters (i.e. succinylcholine, not broken down as quickly as Ach)
Increase anesthetics–bind to Na+ channel while inactivated
Increase H+: blocks Na+ from binding, leading to coma, respiratory acidosis, decrease in renal function
General properties of electrical synapses
- Fast
- pre/post synapses sealed by low-resistance gap junctions
- Connexons (of 6 connexins)= gap junctions
- use little energy, biodirectional
- stimulate multiple cells simultaneously
Properties of chemical synapses–ionotrophic
i.e. nicotinic
- Receptor=ion channel
- NTs activate (i.e. Ach)
- works at medium speed
Metabolism of Ach in synapse
- Made from choine and acetyl coA in presynaptic terminal, uses Ach-H transporter to package
- Degraded by acetylcholine esterase in synapse if too much
Properties of chemical synapses–metabotrophic
(i.e. muscarnic)
- G protein coupled receptor
- Can be very slow
- Example: in cardiac muscle, Ach binds and releases B subunit; this in turn causes K+ channels to open and hyperpolarization (chronotrophic inhibition)
Skeletal muscle synapse structure
Down myeliated axon –> bouton per muscle fiber
This is the motor unit/end plate
Steps of skeletal muscle synapse
- depolarization
- Ca2+ floods cell to release vesicles, fuse vesicles with membrane and have vesicles open above active zone
- Ach binds to ligand channels, causes EPP due to the Na+ current that causes AP
EPP
Due to Ach opening ion channels, local depolarization generated with amplitude that decreases with distance (unlike AP)
Curare
Competitive inhibitor AcH at ionotrophic receptor
i.e. poison darts
Reduced EPP amplitude so no AP
Paralysis
Myeesthenia gravis
Muscular weakness and fatigue
Antibodies compete for Ach receptors (autoimmune disease)
alpha-bungarotoxin
snake venom that causes muscle paralysis
Ach competitive inhibitor
can be used to degrade effects of myesthenia gravis
Botulinus toxin
Blocks the proteins that regulate movements of vesicles to excitatory presynaptic neurons, preventing release of glutamate
Leads to muscle weakness, paralysis, ANS issues
Tetanus toxin
Blocks vesicle movement to inhibitor presynaptic membranes; muscle rigidity, lock jaw
GABA or glycine, inhibitors, are being blocked from release
Organophosphates
inhibit Ach esterase in synapse, leading to parasympathetic activation because too much Ach
SLUDGE: salivation, lacrimation, urination, defecation, GI, emesis
Examples: chemical warfare agents, agricultural insecticides
Use atropine, a competitive inhibitor for muscarinic receptors, to save people
Different types of synaptic connections in nerve cells
Axo dendritic: synapse with dendrite
Axosomatic: synapse with soma
Axoaxonic: synapse with axon
Axospinous: synapse with spine
Long term potentiation
When increased activity of nerve makes moe spines grow, causing increase in postsynaptic intracellular [Ca2+] and EPSP amplitude
Two types neural netwoks
Discrete/spatiall focused: specific, fast, focused, aroused
Widely divergent/diffuse: modulates memory, motor control, mood, etc.
–central core in brainstem
Excitatory synapses (EPSP)
Glutaminergic
- brain visual cortex pyrimidal cell
- local, non-propagated
- glutamate/aspartate
- opens Na/K –> Vm toward threshold –> depolarization
- unlike EPP, low amplitude at single synapse
Inhibitory synapses (IPSP)
- brain visual cortex pyramidal cell
- GABA or glycine
- opens Cl- –> Cl- in cell –> hyperpolarization
- Cl- follows conc. gradient; in CNS neurons, Ecl is near or more negative than the resting potential
Voltage clamping experiments with EPSP
- at -65 mV, an EPSP causes local depolarization
- at Vm=0, EPSP=0; this is because iNa=iK
- Any higher, hyperpolarization and reverse potential
Voltage clamping experiments with IPSP
- at Em=-65, gCl increases and iCl increases, hyperpolarization
- at Em=-71 mV, Ecl=-71, Icl=0, IPSP=0
Spatial summation
several axons send signal to cell
Temporal summation
same axon sends many signals over time
