Resting Potentials and Action Potentials

Lecture 10PSY391S

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).

• 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: MolecularStructure and Gating

All Na+ channels open in APabsolute refractory period.

(No voltage-gated K+ channels in mammalian unmyelinated axons)

(>1 m/s in mammals)

(1-120 m/s)

Synapses and Postsynaptic Potentials

Lecture 11PSY391S

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.

• Exocytosisrelease and diffusion of transmitter.• EPSPs, IPSPs (depending on ions) .• Reuptake or enzyme breakdown of transmitter.

Chemical Receptors

Nicotinic, AMPA Na+ Muscarinic, Dopamine, GABAB

GABAA Cl- Gs, Gi

Ionotropic Receptors

Receptors are now defined by genes

Second Messengers

• 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 12John 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.

• 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?

Synapse Strength

Spines

• Problem: Too many synapsestoo 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 moreplasticity.

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.