IB 132 L4

Central Nervous System (CNS)

brain and spinal cord

Peripheral Nervous System (PNS)

the sensory and motor neurons that connect the CNS to the rest of the body

Afferent

coming into the brain, sensory signaling

Efferent

exiting the brain to the body, motor signaling --> somatic and autonomic

Somatic motor

controls body movement

Autonomic (automatic) motor

unconscious body functions

Breathing

can be both autonomic and somatic

Neuron signal transport pathway

PNS: sensory receptor --> afferent neuron -->

CNS: interneurons -->

PNS: efferent neuron --> muscle, gland, or neuron

Components of neuron

dendrite, cell body, axon hillock, axon, axon terminals --> each neuron is one cell

Axon hillock

initiates action potential

Axon collateral

a branch of an axon from a single neuron

Glial cells - different types of cells supporting neurons

astrocytes, oligodendrocytes, microglia, ependymal cells

-->view diagram

Astrocytes

-help regulate the composition of extracellular fluid in CNS by removing K+ ions and neurotransmitters around synapses

-stimulate the formation of tight junctions in BBB

-sustain neurons metabolically

Blood brain barrier (BBB)

semi-permeable barrier between capillaries and brain that limits entry beyond small molecule diffusion and specific transport mechanisms

Oligodendrocytes

form the myelin sheath of CNS axons

Ependymal cells

line the fluid-filled cavities within the brain and spinal cord and regulate the production and flow of CSF

Microglia

specialized, macrophage-like cells that perform immune functions in the CNS and may also contribute to synapse remodeling and plasticity

What do neurons need to be able to do? What is their function?

sense and communicate quickly

Neuronal signaling

signaling (within a cell) happens via changes to membranes and their permeability to ions

Voltage

electrical potential difference

Voltage across a membrane (Vm)

Vout - Vin

Resting membrane potential

the electrical charge of a neuron when it is not active

--> more negative inside cell than out

Distribution of major mobile ions across plasma membrane of a typical neuron

-extracellular: Na+, Cl-

-intracellular: K+

-->banana in the ocean

-->negative ions (anions) inside the cell that don't move

Passive movement of ions

-chemical gradient

-electrical gradient

Equilibrium potential

the magnitude of the membrane voltage at equilibrium for a particular ion

Chemical gradient

concentration gradient for an ion across the plasma membrane

Electrical gradient

difference in electrical charges between the inside and outside of the cell

Nernst equation

Ecell= 61/Z*log(Cout/Cin)

-->allows you to calculate equilibrium potential for an ion given relative concentrations

Equilibrium potential for Na

highly positive

Equilibrium potential for K

highly negative

Resting potential of membrane --> all different ions together

Erest = -70 mV

-->if we open a channel, ions start moving

Equilibrium potential for Cl

highly negative

Hodgkin-Katz (GHK) equation

Synthesizes contributions from multiple ions to determine resting potential of the cell

Sodium-potassium ATPase pump function

concentrates K+ inside the cell and Na+ outside the cell

--> takes a lot of E, 40% of E produced by cell

PUMPKIN

pump K into cell

Depolorization

getting less polarized (less negative)

Repolarization

getting back to RMP

Hyperpolarization

becoming more negative (further from 0) than the RMP

Graded potentials

-changes in membrane potential that are confined to a relatively small region of the PM

-can be small or large depending on stimulus

-may sum (over space and time) to pass the AP threshold

Excitatory potential/excitatory synpase

-depolarization

-AP more likely

Inhibitory potential/inhibitory synpase

-hyperpolarization

-AP less likely

Threshold value for Na+ channel

-55 mV

Overshoot

getting a positive membrane potential after depolarizing

Ligand gated channels

ligand (molecule) binding affects channel state

Mechanically gated channels

pressure affects channel state

Leakage channel

opens and closes intermittently, randomly

Voltage gated channels

opens at a particular electrical potential and KEY to the AP

Sodium channel

opens as the neuron depolarizes past a particular threshold (-55 mV)

Potassium channel

also triggered by depolarization, but start opening 1 ms later, just as Na+ channels are closing

AP for sodium-potassium pump phases

1) Steady resting membrane potential is near Ek, Pk>PNa due to leak K+ channels

2) Local membrane is brought to threshold voltage by a depolarizing stimulus

3) Current through opening voltage-gated Na+ channels rapidly depolarizes membrane, causing more Na+ channels open

4) Inactivation of Na+ channels and delayed opening of voltage-gated K+ channels halt membrane depolarization

5) Outward current through open voltage-gated K+ channels repolarizes the membrane back to a negative potential

6) Persistent current through slowly closing voltage-gated K+ channels hyperpolarize membrane toward Ek, Na+ channels return from inactivated state to closed state (without opening)

7) Closure of voltage-gated K+ channels returns the membrane potential to its resting value

Action potential

-at resting potential, voltage gated channels are closed

-depolarization induces voltage gated channels to open. First sodium channels, leading to a positive voltage inside cell

-then potassium channels open, repolarizing the cell (and overshooting a bit)

Batrachotoxin

forces Na+ channels to stay open

-->poison dart frog

-->Pitohui bird

Tetrodotoxin

Toxin: very potent sodium channel blocker; blocks action potential propagation in nerve, heart, and skeletal muscle. From puffer fish

ATX II neurotoxin

-sea anemone

-activates voltage-gated Na+ channels

Tetrodotoxin (TTX)

-pufferfish

-blocks Na+ channels

Brevetoxin

-red tide dinoflagellate

-activated Na+ channels

Kaliotoxin

-scorpion

-blocks Na+ channels

Agatoxin

-funnel web spider

-blocks Ca+ channels

Latrotoxin

-black widow spider

-enhances Ach release

alpha-bungarotoxin

-krait (snake)

-blocks Ach receptor

Lidocaine and provocaine (novacaine) effect on APs

binds to Na+ channel and prevents opening

--> small dose and effect depends on location used

AP propagation

local current from opening of ligand-gated channels --> initial site of AP --> RMP depolarized toward threshold by local current --> resting membrane

How come AP does not propagate backward? Why doesn't signal travel towards the axon terminal AND the soma?

membrane is refractory (in refractory period-->the axon membrane needs a moment to recover after firing, and can't fire again within that time period); local current cannot stimulate a 2nd AP

Absolute refractory period

Na+ channels are inactivated --> so even if we hit -55 mV threshold, cannot activate

Relative refractory period

hyperpolarization (potassium overshoot) leads to a relative refractory period when it is harder to reach threshold

-->sodium/potassium ATPase restores high extracellular Na+

What would happen if you depolarized the center of an axon?

do get APs firing in both directions, no refractory period holding it back

Larger diameter neuron

faster action potential, lower resistance

Mylen sheath

-Coating of neural fibers with insulating fatty sheath improves efficiency of message transfer --> faster

-allows for saltatory conduction, jumping from node to node

Node of Ranvier

A gap between successive segments of the myelin sheath where the axon membrane is exposed, site of APs

Inactive node

node at RMP

Other node

node to which depolarization is spreading and regenerating an AP