Transcript Resting Potentials and Action Potentials

Resting Potentials and Action
Potentials
Lecture 10
PSY391S
John Yeomans
Special Properties of Neurons
• Excitability--Action Potential in Axons.
• Conduction--Action Potential in Axons.
• Transmission--Synapses, Electrical &
Chemical.
• Integration--Postsynaptic Cell.
• Plasticity--Presynaptic Terminal and
Postsynaptic Membrane.
Resting and Action Potentials
Pumps Exchange Ions
• All cells have pumps and resting potentials
(-40 to -90 mV).
• Pumps use ATP to exchange ions.
• Na+/K+ pump: 3 Na+ exchanged for 2 K+.
• Ca++ pump: Keeps powerful Ca++ ions
out.
Concentration of Ions and
State of Channels at Rest
-65 mV
Concentrations maintained by Na+/K+ and Ca++ pumps.
Potentials
• All potentials result from ions moving across
membranes.
• Two forces on ions: Diffusion (from high to low
concentration); Electrical (toward opposite
charge and away from like charge).
• Each ion that can flow through channels reaches
equilibrium between two forces.
• Equilibrium potential for each ion determined by
Nernst Equation.
• K+ make - potentials; Na+ make + potentials.
Nernst Equation
• EK+ = +58 mV log10 ([K+] outside/[K+] inside).
(+58 mV for room temperature, squid axon).
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EK+ = 58 mV log10 1/20 = -75 mV.
ENa+ = 58 mV log10 10/1 = + 58 mV.
ECl- = -58 mV log10 15 = -68 mV.
ECa++ = +58 mV log10 10,000 = +220 mV.
Resting Potential Results from
Passive K+ Channels and EK+
• At rest, membrane potential is -60 to -70
mV in most neurons. Why?
• K+ is most permeable, due to leak of K+
through passive K+ channels.
• Therefore, K+ ions leave, making the
inside more negative.
Action Potential Results from
Voltage-gated Na+ Channels
ENa+ = +58 mV

EK+ = -75 mv 
Closed!
Action Potentials
• Only neurons and muscles have action
potentials (not all neurons).
• Due to voltage-gated Na+ channels.
• Most in axons, at initial segment (axon
hillock) and nodes of Ranvier. A few in big
dendrites where depolarizations need a
boost.
• Channel ionic currents are studied by
voltage clamps and patch clamps.
Voltage Clamp
• Used to measure ion currents in squid giant
axons (Hodgkin & Huxley).
• Study single ion by changing ions in axon.
• Hold voltage constant by injecting current with
large electrode. Measured current I.
• Measured Na+ or K+ current during action
potential: INa+ = V/R = K/R ~ Na+ conductance.
• Measure “channel” permeability changes.
• Predicted action potential changes from Nernst
Eq and channel permeabilities.
Single Channels
Study electrical properties,
Ionic properties,
Pharmacology (toxins, agonists, antagonists)
Molecular biology (mutant channels)
Voltage-gated Na++
Channel: Molecular
Structure and Gating
(>1 m/s in mammals)
All Na+ channels open in APabsolute refractory period.
(No voltage-gated K+ channels in mammalian unmyelinated axons)
(1-120 m/s)
Synapses and Postsynaptic
Potentials
Lecture 11
PSY391S
John Yeomans
Release and Ca++
• Transmitter is synthesized and stored in
vesicles.
• Action potential opens voltage-gated Ca++
channels near release sites.
• Ca++ activates proteins that move vesicles to
release sites.
• Exocytosisrelease and diffusion of transmitter.
• EPSPs, IPSPs (depending on ions) .
• Reuptake or enzyme breakdown of transmitter.
Chemical Receptors
Nicotinic, AMPA Na+
GABAA Cl-
Muscarinic, Dopamine, GABAB
Gs, Gi
Ionotropic Receptors
Receptors are now defined by genes
Second Messengers
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cAMP and cGMP, IP3, DAG (G-coupled)
Ca++, etc.
Kinases (dozens, e.g. A, CaMK)
Gene transcription (CREB)
Plasticity
Retrograde messengers NO and CO.
Other Receptor Types
• Steroid receptors--Lipophilic molecules
pass through membrane to act in neurons.
• Tyrosine kinase receptors--NGF activates
enzymes and kinases.
• Slower growth effects.
Summation
PSPs
• Excitatory: Na+ or Ca++ entry.
• Inhibitory: K+ efflux or Cl- entry.
• Also blocking open channels (e.g. rods
and cones).
• Slow potentials: seconds to hours.
Integration of Potentials
Lecture 12
John Yeomans
PSY391S
Computation in Single Neurons
• Thinking requires complex computation.
How?
• Neural computation occurs in postsynaptic
cells, by integration of PSPs, and by
changes in synapses.
• We still have no idea how thoughts are
represented in neurons or circuits, only
rough ideas of which brain regions are
important.
Integration in the Cell and Axon
PSPs decay with distance.
Integration occurs at axon hillock.
Synapses on Soma, Dendrites and
Spines
Thousands of synapses, of many types, on each output neuron.
Synapse Strength
• Strongest near axon, usually inhibitory.
• Next strongest on soma and proximal
dendrite shafts.
• Weakest synapses on spines, usually
excitatory.
• Larger neurons usually have more
synapses, more spines. Why?
Spines
• Problem: Too many synapsestoo much
ion leakage along dendrites.
• Solution: Place synapses on isolated
spines.
• All spine synapse have equal access to
dendrite shafts.
• Spine shapes change in minutes:
mushrooms less, slivers moreplasticity.
Plasticity
• Facilitation and depression of PSPs.
• Presynaptic changes: transmitters,
vesicles, release, retrograde NO.
• Postsynaptic changes: Receptors can be
added and subtracted. Channels can be
phosphorylated;
• Second messengers and kinases can
change postsynaptic response;
• Spines can grow or shrink; New proteins.
Integration of Brain Potentials
• Most recordings are extracellular, or
outside brain. Averages across many or
millions of neurons.
• Electrode size and distance determines
how many neurons are measured.
• Human studies are mainly from surface of
brain. Brain-waves are correlated with
thoughts (Dreams, meditation, stimuli).
Human Potentials
• Strong potentials in muscles--EMG, ECG
(electromyogram and electrocardiogram).
• Weaker potentials from brain--EEGs.
• Evoked potentials allow study of changes.
• Computer averaging allows study of deep
brain potentials: Event-related potentials in
sensory systems and cognition.
EEG and ERP
Electroencephalogram
• Shows widespread activity of brain, mainly
from PSPs.
• Sleep stages, waking, slow wave, REM.
• Most intense in seizures of different types,
petit mal, grand mal etc.
• Can find lobes that are most active (e.g.,
occipital for alpha waves, temporal or
frontal lobe or for seizures).
Event-Related Potentials
• Warning and CNV: Cortex mainly.
• I-VI : Brain stem auditory paths.
• No-P3 : Cortical processing of auditory
stimulus. Primary to association areas.
• Temporal resolution better than spatial
resolution.
• Brain imaging (fMRI) localizes thoughts
better, but not to neurons.