PNB 2774 Neurons and Action Potentials

membranes exhibit electrical behavior

• insulator → membranes typically prevent charge passage

• conductor → membranes can allow charge passage

• active/passage behaviors → membrane electrical behavior — whether “active” (channels opening and closing, pumps working) or passive (membrane behaving like components of a circuit) — is responsible for signaling in neurons, muscle, and other cell types

ion flux through ion channels

• protein pores in membrane, classified by:

  • ion selectivity → K⁺, Na⁺, Ca²⁺, etc

  • gating (“opening”) mechanism → leak, voltage, or ligand (a chemical)

  • rate/duration of activity → fast/delayed; transient/long-lasting, etc

  • resting potential large maintained through activity of K⁺ leak channels

    • various classes → K_ir inward rectifiers, K2P pore domains; etc

nernst equilibrium

E_ionx = the electrical potential (“voltage” V_m) at which the diffusional flow of an ion one way is balanced by electrostatic attraction in the other (voltage in millivolts mV)

nernst equation

E_ionx = RT/zF ln{[X]_o/[X]_i}

equilibrium potential

the membrane potential at which a given ion type’s net flux is zero

nernst potential

describes the membrane potential that a single ion would produce if the membrane were permeable to only that ion

“reversal potential”

the membrane potential at which the flux of a given ion type reverses from inward to outward

depolarization

changing membrane potential to be more positive (more +) (EPSP)

hyperpolarization

changing membrane potential to be more negative (more -) (IPSP)

repolarization

returning membrane potential towards rest potential (from either a depolarized or hyperpolarized state)

equilibrium 

an unchanging state that remains so without manipulation

steady-state

an unchanging state that remains so only by constant input/output

GHK equation

predicts membrane potential that results from the contribution of all ions that are membrane-permeant (can cross the membrane)

• multiple ion case → V_m is somewhere between the most negative E_x (usually E_K) and the most positive E_x (usually E_Na)

  • if a cell is permeable to multiple ions, V_m is a weighted average of the E_x for each permeable ion

• “one-ion” case (GHK reduces to nernst) → V_m approximates E_x of the most permeant ion

types of cell in nervous tissue

• neurons

• neuroglia

neurons 

nerve cells that are capable of initiating and conducting electrical activity throughout the body

neuroglia

cells that support the neurons

function of nerve cells

communication and control of body functions

parts of a neuron

• dendrites

• cell body

• axon

dendrites 

receive incoming signals; passive, graded synaptic potentials

cell body

“integrates” multiple incoming signals via summation

axon

carries the output signal; an “all-or-none” action potential

graded potentials

• passive (or “electrotonic”); like a cable

• degrade with distance and time

• variable amplitude and variable duration, hyper and de-polarizing sign

• sub-threshold: no AP

action potentials

• active; self-regenerating

• no decrement with distance: they maintain the same amplitude

• “all-or-none;” brief (1 ms), fixed duration: largely depolarizing

• supra-threshold

similarities between graded and action potentials

• voltage changes in membrane

• propagate down neuronal “processes”: axons/dendrites

• transient events

action potentials (“firing”/”spikes”)

an “all-or-none” wave of elevated potential that will result in some “action” on the part of the cell

• actions → vesicle release, muscle contraction, signal propagation

• also called “spikes” because of the spike in the potential vs time graph

• a cyclical process of channel opening and closing

AP sodium channels 

• have two gates: activation (open/close) and inactivation (block/unblock)

• Na⁺ channels open → sodium flows in; cell depolarizes

• with positive voltage → Na⁺ channels activate fast; Na⁺ channels inactivate slow

AP steps

• resting membrane potential

• depolarizing stimulus

• membrane depolarizes to threshold. voltage-gated Na⁺ channels open quickly and Na⁺ enters cell. voltage-gated K⁺ channels begin to open slowly

• rapid Na⁺ entry depolarizes cell

• Na⁺ channels block and slower K⁺ channels open

• K⁺ moves from cell to extracellular fluid

• K⁺ channels remain open and additional K⁺ leaves cell, hyperpolarizing it

• voltage-gated K⁺ channels close, less K⁺ leaks out of the cell

• cell returns to resting ion permeability and resting membrane potential

AP potassium channels 

K⁺ channels have one gate: activation only 

• K⁺ channels open → potassium flows out; cells repolarize

• with positive voltage → K⁺ channels activate slow; K⁺ channels don’t inactivate

AP ion permeabilities

• permeability to K⁺ and Na⁺ changes dramatically during the course of an AP

• P_K:P_Na:P_Cl

  • AP peak → 1/20/0.15

  • resting potential → 1/0.03/0.15

• with negative voltage:

  • Na⁺ channels de-activate fast

  • Na⁺ channels un-activate slow

  • K⁺ channels de-activate slow

• P_K dominates for repolarization and afterhyperpolarization (AHP)

the axon

• the “trigger' zone” for AP initiation

• high density of voltage-gated sodium channels that trigger APs

• ultimate “output” of dendritic integration

AP myelination

• myelin “sheath”: 10-160 concentric “wrappings” of glial membrane around axon

• distance between nodes: from a few hundred µm to several nm

• myelin alters distribution of Na⁺ and K⁺ channels

• myelin results in “saltatory conduction”

• myelination can increase the speed of conduction by a factor of 100

• myelination by glial cells called:

  • oligodendrocytes in CNS

  • schwann cells in PNS

synapse

a point of connection between two neurons

• the basic structural mechanism of communication between neurons or to effector cells (muscle, heart, glands)

electrical synapse

• bi-directional signaling

• direct signal coupling

• second cell mirrors first one

• gap junctions

chemical synapse

• anterograde (forward direction) signaling: pre-to-post synaptic

• post synaptic response depends on receptors

• pre → vesicles hold neurotransmitters

• post → receptors

• post-synaptic response depends on receptors

vesicle exocytosis

• filling (with neurotransmitter)

• vesicle translocation

• docking (putting vesicles in the right place)

• priming

• fusion with membrane (signals from Ca²⁺)

vesicle endocytosis

• vesicle membrane transmissions

• coating with clathrin (usually)

• fission of coated vesicle from membrane

• uncoating from clathrin

• recycling (by several paths)

v-SNAREs

• vesicular

• many kinds. key one is synaptotagmin: Ca²⁺ sensor

t-SNAREs

“target” (terminal membrane)

ligand-gated ion channel

• fast synaptic transmission (<100 ms)

• opens ion channels (typically)

• receptor and channel part of same protein

• little amplification (1 (or 2) NT opens one channel)

• “ionotropic” receptor

G protein-coupled receptor

• slow synaptic transmission (>100 ms)

• opens or closes ion channels, among other things

• receptor and channels (if used) are separate proteins

• amplification (1 NT may affect many channels)

• “metabotropic” receptor → 2nd messengers

a generalization (to all ion channels)

• opening of neurotransmitter receptor drives V_m towards E_x for that channel

• depending on E_x, the effect may be inhibitory or excitatory

termination of action

• diffusion away from synapse

• re-uptake by pumps and transporters

• cleavage by pumps

other neurotransmitters

• purines → AMP and ATP

• gases → NO, CO, H₂S

• peptides → substance P and opioid peptides

• lipid-derived → eicosanoids, cannabinoids