III. NEUROPHYSIOLOGY A) REVIEW - 3 basic ideas that the student must remember from chemistry and physics:

(i) CONCENTRATION measure of relative amounts of solutes in a solution. * Measured in units called MOLES

(ii) DIFFUSION = things always move from an area of high [ ] to an area of low [ ]

“Go down a concentration gradient" (iii) RATE OF DIFFUSION (that is, how fast do they flow) depends on the CONCENTRATION GRADIENT (among other things, like temperature, etc.). - Cell uses Concentration Gradients to move solutes across the PM

B) ELECTROMAGNETIC FORCE (or ATTRACTION). Particles with opposite charges (positives and negatives) attract each other, while particles with the same charge repel each other.

*any barrier between the positive and negative particles will cause a POLARITY. The barrier is RESISTANCE (it resists the flow of particles).

- The barrier (resistance) gives us an ELECTRICAL POTENTIAL (potential energy, or potential to do work). When the particles move, they can do work!

The negative side is attracted to the positive side, and vice-versa, causing a force or POTENTIAL for movement or work. If we put a hole in the barrier, the particles will go rushing across. We can measure the difference in charge between the sides = VOLTAGE. C) ELECTROMAGNETIC GRADIENT and ELECTRICAL CURRENT.

How strong is the attractive force; that is, how DIFFERENT are the positive and negative sides (VOLTAGE). Is one side a lot more “positive” than the other, or just slightly?

This affects how quickly the particles move once we lower resistance. Particles move down an electromagnetic gradient similar to how they move down a concentration gradient.

Electrical Current = the movement of electrons. When they move, they can do work!

*OHM’s LAW: current is directly proportional to gradient (the more different the 2 sides are, the faster the particle will flow if I put a hole in the barrier).

* So, there are 2 "gradients" pulling on any charged particle: concentration and electromagnetic. Which way “A” moves in the diagram depends on which gradient is steeper! They can work in the same direction, or opposite directions.

* Do you see that diffusion will happen REALLY fast if both gradients are in the same direction?

Where are we going with this? - in the next section, we'll be using these concepts to conduct electricity down the neuron. IRRITABILITY or EXCITABILITY: ability to respond to stimuli with ELECTRICAL CURRENT (FLOW OF e-; an electrical charge).

D) GENERATING AND MAINTAINING ELECTRICAL CURRENT ON A NEURON - OVERVIEW: We saw in the last section that there are 3 steps to electrical current on the neuron:

(i). Neurons build up a potential across their plasma membrane - MEMEBRANE POTENTIAL (ii). If stimulated, the neuron lowers resistance by opening channels and letting ions - Na+ and K+, flow down their concentration and electromagnetic gradients - DEPOLARIZATION (iii). If the depolarization is strong enough, this generates electrical current (an ACTION POTENTIAL) on the plasma membrane of axon. The AP will then be PROPAGATED to the axon terminal, assuring one-way flow down the PM via HYPERPOLARIZATION. The AP is a signal to another cell.

- Steps: 1. RESTING MEMBRANE POTENTIAL (RMP)

- RESTING MEMBRANE POTENTIAL (RMP) - at “rest” (when the cell is not “working”, or conducting electricity), there is a certain POTENTIAL across the plasma membrane. What causes this potential?

* Inside the cell there are (-) charged proteins, keeping the inside of the cell slightly more (-) than the extracellular fluid. * The extracellular fluid contains a high concentration of Na+.

This potential can be measured (= it’s CHARGE) = ~-70mV (between -40 & -90 mV), which is due mostly to potassium.

* Why “negative 30”?? Because we are measuring the inside compared to the outside. The inside is “70 mV LESS”.

* In general, Na+ wants to move into the cell, and K+ wants to move out, down their [ ] gradients. Also notice that Na+ wants to move into the cell down an ELECTROMAGNETIC gradient, as the inside is more (-) than the outside. Sodium will rush in if permitted. We will use this in the next step.

* In order to maintain this RMP, the system depends on the membrane NOT being leaky to Na+ and K+ (or else, over time, the RMP would disappear). However, some does leak through!

** offset by the SODIUM-POTASSIUM PUMP, which acts to make the membrane “appear” non-leaky (NOT SHOWN ON IMAGE).

* SUMMARY: 1. What causes the RMP? Different permeability of the membrane to Na+ and K+. Cell is positive on the inside due to proteins, while the extracellular fluid has a relatively positively charged due to sodium.. 2. The sodium-potassium pump maintains the RMP. 3. In general, Potassium is responsible for the potential of -70mV.

2. DEPOLARIZATION - DEPOLARIZATION: stimulus causes a DECREASE in polarity (depolarization). For neurons, this means a decrease in polarity from RMP.

* How do this? LOWER RESISTANCE of membrane = put holes in it = open ion channels!

- PROTEIN CHANNELS: ”doorways” through the plasma membrane of the cell; can be closed or opened, thereby increasing or lowering resistance to flow of ions ("ion flux").

** IMPORTANT POINT: anything I do to lower resistance (like, say, put holes in the barrier) increases flux, and may lead to electrical current!!!!

* There are several types of these channels, based on how they are opened. For the depolarization step, we will be using one of them:

CHEMICALLY-GATED (Ligand-gated) ION CHANNELS: open or close when a chemical (= a NEUROTRANSMITTER) binds (= attaches) to it. - Depolarize: make the polarity LESS.

* Immediately, potassium diffuses out (through different channels), REPOLARIZING the membrane. Why does Sodium move into the cell before potassium move out? Remember: sodium is smaller, and is going down 2 gradients, while potassium is larger and only diffusing down its concentration gradient!

- Problem: we just lowered the concentration of sodium on the outside of the PM, and of potassium on the inside of the cell.

* Solution: the Na-K Pump re-establishes the concentration of Na+ and K+ automatically, using ATP!

- Depolarizations may cause an ACTION POTENTIAL on the membrane (next step), so anything I do to cause the membrane to change permeability (depolarize) is causing it to conduct electricity!

* What is the original stimulus? The ligand! A chemical called a NEUROTRANSMITTER opens chemically-gated sodium channels on a neuron at the point of stimulation; that is, the neurotransmitter IS the stimulus!

** NEUROTRANSMITTER - any chemical that causes chemically-gated channels to open. Several types (see later); ACh is most common.