Lecture 3 + Assignment 3 Flashcards
A.P. speed compared to electricity
- electricity = 1/2 speed of light
- A.P. speed slower
Leaky, sticky, and thin
- all make a.p.s move slower
Leaky = low membrane resistance
Rm
Sticky = high membrane capacitance
Cm
Thin = high axial resistance
Ra
Membrane resistance / Rm
- leakiness
- like a balloon with a hole
Rm = resistance of the membrane
Membrane capacitance / Cm
- stickiness
- ability of membrane to store charge
- if it can’t store charge well, sticks to ions on the outside due to attraction
- makes them travel slower
Cm = capacitance of the membrane
Axial resistance /Ra
- thin = hard to flow through
- how easy it is for ions to flow through
Ra = resistance of the axon
Invertebrates avoiding leaky/sticky/thin
- evolved wider axons
- they take up more space
Vertebrates avoiding leaky/sticky/thin
myelin
- reduces axon leakiness and stickiness
saltatory conduction
- jumping between nodes of Ranvier
- makes conductance speed faster
Myelin in CNS vs. PNS
+ Nervous system path
Oligodendrocytes
- in CNS
- connect to multiple axons
Schwann cells
- in PNS
- connect to one axon
myelin -> glial cells -> oli -> multiple axons
Theodor Schwann
Discovered schwann cells
supported cell theory
“all living things are composed of cells and cell products”
Multiple sclerosis
- autoimmune disorder where virus with an antigen that looks like myelin gets degraded as well
- Epstein-Barr virus
- myelin attacked/degraded by immune system
- slow action potentials
- also forms sclerosis scar tissue which slows a.p.s
- lose feeling then it comes back
- nervous system fights back to repair glial cells/myelin
- first symptoms vision, tactile, balance, speech
- 20-40 years old
- 2x prevalence in women
- genetic factors (twin studies)
1/1000 ppl
Guillain-Barre syndrome
- similar to MS but in PNS
- antibodies attack myelin schwann cells
1/100 000 ppl
- symptoms: paresthesia, paralysis, loss of sensation
- movement difficulty starting in the legs moving up
- rapid onset, recovery after weeks or years
Neuron doctrine vs. reticular theory
Golgi
- reticular theory
- neurons all connected through giant network
Santiago Ramon y Cajal
- neuron doctrine
- separate by nearby neurons
Synaptic cleft
20-40 nm wide
beneath the resolution of conventional light microscopy
1nm = 10^-9 m
Otto Loewi - heart in a jar
- do heartbeat in one jar
- slow heartbeat
- makes heart in other jar also slow down
- indicates chemical transmission through synapses
bc vagus nerve releases something into the saline fluid
- did this experiment
- used frog hearts
- dreamt it up then scribbled it down but couldn’t read the stuff
Evidence of quantal transmission
- smallest possible depolarization of 0.4 mV
- quantal packages during synaptic release
Bernard Katz
- found evidence of quantal transmission
- 1911-2003
Resting synapse
- neurotransmitters in synaptic vesicles
- presynaptic axon connects to postsynaptic dendrite
axon terminal = synaptic bouton
- voltage-gated calcium ion channel closed
Active synapse
neurotransmitters in vesicles leave the cell (exocytosis)
bind to ligands
opens ligand-gated ion channels when they bind
- opens voltage-gated calcium ion channels
Ca goes OUT
Calcium leaving the axon terminal
Ca pump lets it out of the cell as 2H enters
- uses ATP hydrolysis
Na/Ca exchanges one for another
Mechanisms of transmitter exocytosis
- vesicle docks
- SNARE complexes form to pull membranes together - vesicle to axon terminal membrane
- exiting Ca binds to synaptotagmin on vesicle
- Ca-bound synaptotagmin catalyzes membrane fusion and teurotransmitter releae
Gruber prize in neuroscience - 2012
+ how many neurotransmitters discovered
Lily Jan and Yuh Nung Jan
- discovered that peptides can be neurotransmitters
over 100 neurotransmitters discovered
Small molecule amino acid neurotransmitters
Glutamate
- most common excitatory nt
GABA
- most common inhibitory nt in cerebral cortex
Glycine
- common inhibitory nt in brainstem/spinal cord
Glutamate receptor channel
- glutamate binds
- channel opens and lets Na in
= excitatory
has same permeability of K out as Na in (g=g)
Na has a larger driving force in so net current inward = negative current
GABA receptor channel
- GABA binds
- channel opens and lets Cl in
- selectively permeable to Cl
= inhibitory
Driving force equation
I = g(Vm - E)
I = current of ion
g = membrane conductance
Vm = membrane potential
E = equilibrium potential
Vm - E = driving force on ion
+/- Current
(+) current
= outward (+)
- cell loses (+) charge or gains (-) charge
GETTING MORE (-)
(-) current
= inward (+)
- cell loses (-) charge or gains (+) charge
GETTING MORE (+)
Axon hillock
where axon attaches to the cell body
EPSP
- glutamatergic
- depolarization
IPSP
- GABAergic
- hyperpolarizaion
Spatial integration of EPSPs
lambda = length constant = √rm/ra
Vx = Voe^-(x/lambda)
Vx = membrane potential
x = distance
Temporal integration of EPSPs
tau = time constant = rmxcm
Vt = Voe^-(t/tau)
Vt = membrane potential
t = time
Spatiotemporal integration
- spatial and temporal EPSPs
Patch clamp - nobel prize
Nobel prize in physiology or medicine - 1991
Neher and Sakmann
- invented patch clamp
- discovered opening and closing of single ion channels
Patch clamp - technique
- pipette over ion channel
- suction doesn’t allow other ions to enter
Cell-attached recordings
- just take recordings with suctioned separate environment
=microscopic currents
- reveals characteristics of different channels
Whole-cell recordings
- strong pulse of suction to make cytoplasm continuous with pipette (breaks membrane)
Inside-out
- take a chunk and membrane closes behind it
- cytoplasm facing out
- can change medium inside cell
Outside-out
- take a chunk and membrane closes behind it
- rips twice and folds back together in pipette
- membrane facing out
Fast vs. slow axonal transport rates
Fast axonal transport occurs at a rate of up to 400 mm/day.
- uses molecular motors like kinesin, dynein
Slow axonal transport occurs at a rate of 0.5–5.0 mm/day.
Anterograde vs. retrograde transport directions
Anterograde axonal transport towards axon terminal.
Retrograde axonal transport towards cell body.
Glutamate = not axonal transport
- synthesized in presynaptic cytoplasm
- packaged into synaptic vesicles by vesicular glutamate transporters, aka VGLUTs
- vesicles are then transported into cells by excitatory amino acid transporters, aka EAATs
