BIO408 - TT1

Stephen Kuffler

Formed the first department of Neurobio in Harvard in 1966

Hippocrates

Idea of the brain as center for emotions and intelligence

Aristotle

Said the heart as centre of thought and emotions and the brain acts like a radiator

Galen

Brain is similar to the heart and so, its ventricles are like chambers of the heart 

Vesalius

Still talked about the humoural theory - focus on ventricles

Descartes

Focus on ventricles - idea that they connect to control movement

18-19th Century Neurosci

Change from humoural theory to modern views due to increase in scientific process and methods

18th-19th Century Neurosci lead to the findings of

• nerves as electrical wires

• Different brain

• Neutron doctrine - Cajal

Ventral Areas control

Motor functions

Dorsal Areas control

Sensory functions

4 Basic types of signal potentials

Resting membrane potentials, receptor potentials, Synaptic potentials, action potentials

Resting Membrane potential

baseline for all cells - don’t carry info and sre ‘static’

Receptor potentials

small amplitudes that are sensory inputs turned into electrical inputs → touch to signal

Synaptic Potentials

Synapse at neurons where its information from one neuron/area to another

Action potentials

largest amplitudes and are fixed in waveform → quickest form of signalling

Neural signals occur when

ions create electrical charges that move by ion [C] gradient

Ion levels in a cell

• K = 100mM in side, 5mM out

• Na = 15mM inside, 150mM out

• Cl = 13 mM inside, 150mM out

• Ca = 0.0002mM inside, 2mM out

Active transporters

• ATPase pup

• Ion exchanger

Need energy from ATP or [C] gradients of other ions 

ATPase Pumps

Na/K pump = low Na in, high K in

Ca²⁺ pump = low Ca in

How does the Na/K ATPase pump work?

1. conformation change that allows Na binding and ATP binds

2. pump becomes phosphorylated → P only and pump closed

3. conformational change to release Na out and K binds from outside

4. Pump phosphorylated and loses P

5. ATP binds to let K inside and Na binds again 

6. restart

How many Na/K get bound/let out or in?

3 Na out and 2 K in

How do Ion exchangers work?

Use the energy of the Na/K [C] gradients made from ATPase pumps

What are the two main categories of ion exhangers?

Antiporters and co-transporters

What are two types of Antiporters and how do they work?

• Na/Ca exchanger - keep Ca low inside

• Na/H exchanger. -regulates pH - H out

These work in opposite directions, where one ion goes inside, and the other out

What are the 3 types of co-transporters and how do they work?

• Na/K/Cl co-transport - Cl inside

• K/Cl - co-transport - regulates Cl out

• Na/NTs co-transport - synapses

These work by ions moving in the same direction in or out

How are ion gradients established?

• ion gradients 

• ion channels

Why ion channels?

They allow ions to diffuse down their [C] gradients high to low and are selectively permeable

Is resting membrane pot Vm = 0?

NO! thats why we have ion channels, they control RMP

What if we had no ion channels?

Then no e- potential - so no resting membrane

How is the RMP created?

K moves across [C] gradient - chemical pot

Then ± charges re-distribute and causes to build up e- potential around membrane

will lead up and countinue to flow until eq.potential of K = negative

then Na also flows and has + potential(not exactly eq.pot in the cell)

Chemical potential is the

flow of ions

Electrical potential is the

flow of charges

The Nernst Equation

z = ion charge

ion out = outside ion [C]

ion in = inside ion [C]

If there was only one type of ion channel then resting

Vm equals to eq.potential of that ion

What is the E ion for the major 3 ion types?

K = -80 mV

Na = 62 mV

Cl = -65 mV

The smaller the ion-out/ion-in ratio is, the

more negative the Eion is

Goldman=Hodgkin-Katz equation

Vm = 62log(permeability out of ions)/(permeability of ions in)

What is an assumption of Goldman equation?

Cl = 0 

In a cell, Vm is closer to the eq.potential of the ion that is

more permeable

if PK/PNa = 40, then

Vm = closer to K, so more (-)