Exam 2 Lesson 4 Neuro

Neuronal cell membrane at rest

has a cloud of positive charges on the outer surface and a cloud of negative charges on the inner surface

Separation of charge

maintained by the lipid bilayer and the Na-K pump

Charges separated at rest

maintained because the membrane acts as a barrier to diffusion no diffusion can occur through the membrane unless an ion channel is opened

Membrane potential Vm

the electrical potential or voltage difference across the membrane created by charge separation defined as Vm = Vin-Vout

Resting membrane potential RMP

the membrane potential of a cell at rest usually ranges from -60 mV to -70 mV

Electrical signaling

results from brief changes in the RMP caused by electrical currents ions flowing across the cell membrane

Depolarization

changes in membrane potential that result in a less negative more positive membrane potential

Hyperpolarization

changes in membrane potential that result in a more negative membrane potential more negative than the RMP

Passive responses of the membrane

changes in membrane potential that do not lead to the opening of channels and are referred to as electrotonic potentials

Electrotonic potentials

the size of the change in potential is proportional to the size of the current pulse

Threshold

depolarizing events that reach this point will lead to action potential generation

Direction of current flow

defined by the net movement of positive charge

Ion distribution

unevenly across the cell membrane

Na and Cl ions

concentrated outside the cell membrane

K ions

concentrated inside the cell membrane

A- ions

various proteins amino acids concentrated on the inside such molecules cannot cross the membrane

Ionic concentrations in vertebrate nerve cells

typically much lower than in the giant squid axon

Ratio of external to internal ion concentrations

are similar and therefore the concentration gradients are similar

Resting channels

are not voltage-gated and are typically open

Resting potential at rest

expected to be very close to the electromotive force for K+ the ion with the largest membrane conductance

Glial cells RMP

typically about -75 mV

K ions at rest

tend to diffuse down their concentration gradients moving from the inside to the outside

K diffusion effect

net positive charge accumulates on the outside attracting negative charges on the inside

K+ flux out of the cell

is self-limiting due to electrical potential difference generated by growing charge separation

Ions subject to two forces

1 a chemical driving force and 2 an electrical driving force

Equilibrium for K EK

the point where the electrical driving force on K+ will be balanced by the chemical driving force

EK equilibrium potential

outward movement of K+ driven by concentration gradient equals inward movement of K+ driven by electrical potential difference

Glial cells resting open channels

permeable only to K+

Equilibrium potential

the electrical potential generated across the membrane at electrochemical equilibrium predicted by the Nernst equation

Equilibrium potential definition

defined in terms of the potential difference between the outside and the inside of the cell

High K+ inside

an inside-negative potential is measured across the membrane

Nernst equation for K at 25C general

EK = 58 mV/z log K+o/ K+I

Valence for K+

z = +1

Nernst equation for K at 25C specific

EK = 58 mV log K+o/ K+I

Calculated EK using 20 and 400 concentrations

-75 mV

Nernst equation prediction linear relationship

a slope of -58 mV per tenfold change in the K+ gradient when Vm is plotted against log K+ gradient

Condition for no membrane potential

if membrane permeable only to K+ and K+ is replaced by Na+ unless membrane permeable to Na+

Membrane potential if permeable to Na+ with 10mM outside 1mM inside

• 58 mV

Membrane potential if permeable to Cl- with 1mM outside 10mM inside

• 58 mV

Vm set at EK

yields no net flux of K+

Vm more negative than EK

K+ will move against its concentration gradient moving from outside to inside

Neuronal cell membranes permeability

permeable to K+ Na+ and Cl-

Membrane permeable to more than one ion

such ions contribute to the driving forces acting on all permeable ions

Na+ ions when membrane permeable to Na+

driven in by 1 the chemical gradient for Na+ and 2 the negative electrical potential across the membrane

Influx of Na+

would depolarize the cell but only slightly from the equilibrium potential for potassium EK

ENa value

+55 mV

Vm not near ENa

due to many more resting K+ channels than Na+ channels in the membrane

Vm depolarizes away from EK

K+ is no longer in equilibrium

What happens to K+ when Vm depolarizes

K+ moves out of the cell trying to counter the influx of Na+

New resting potential

reached when the increased outward movement of K+ is balanced by the inward movement of Na+

Ion flux equation

electrical driving force + chemical driving force x membrane conductance

Cole and Curtis discovery

ion conductance across the membrane increases greatly during an AP

AP ion flux evidence

Cole and Curtis discovery was the first evidence that an AP results from changes in the flux of ions through channels

Hodgkin and Katz insight

observed that AP amplitude is reduced when external concentration of sodium is lowered

Action potential AP

the primary electrical signal generated by neurons

AP origin

arises from changes in membrane permeability to specific ions

AP ion changes

rapid and transient rise in sodium permeability followed by a slower and prolonged rise in potassium permeability for most axons

AP initiation

when the neuronal membrane potential becomes more positive than threshold

Permeabilities during AP

both are voltage-dependent increasing as the membrane potential depolarizes

Ionic permeability evidence

comes from voltage clamp studies

Understanding permeability

requires controlling membrane potential and simultaneously measuring permeability changes

Problem studying AP permeability

any change in Vm producing an AP would lead to more uncontrolled changes in Vm

Voltage clamp method

technique that allowed scientists to clamp the voltage at a desired value and observe changes in membrane conductance

Positive feedback mechanism in AP

drives the membrane potential to generate an AP making it impossible to stabilize the membrane potential

Voltage clamp effect on channels

interrupts the interaction between membrane potential and the opening and closing of voltage-gated ion channels

Goldman equation

takes into account the concentration gradient and the relative permeability of several ions more typical of a real neuron

Goldman equation vs Nernst equation

extended version of the Nernst equation needed when membrane is permeable to more than one ion

Goldman equation reduction

reduces to the Nernst equation if the membrane were permeable to K+ only

Vm if equally permeable to K+ and Na+

0 mV or some intermediate value if unequally permeable

Hodgkin and Huxley technique use

used the voltage clamp technique to understand the permeability changes underlying the AP

HH tested hypothesis

membrane potential-sensitive Na+ and K+ permeability changes are both necessary and sufficient to produce an AP

HH research question 1

Do neuronal membranes have voltage-dependent permeabilities

HH method to test voltage-dependence

asked if ionic currents flow across the membrane when the potential is changed

Hyperpolarization by 65 mV

results in a brief capacitive current or a redistribution of charge across the membrane

Ion flow after hyperpolarization

very little ion flow across the membrane

HH observation during depolarization

a very different response from that observed during hyperpolarization

Depolarization ionic currents observed by HH

a rapid rising inward current followed by a more slowly rising delayed outward current after the capacitive current

Membrane permeability of axons

established to be voltage-dependent based on the observation that depolarization elicits ionic currents

Ionic permeability characteristic

is voltage-sensitive or voltage-dependent

Current flow negative Vm

no appreciable current flows at negative membrane potentials below the resting potential

When the Vm (membrane potential) than its reverse potential

current flows and reverses its polarity at more positive potentials

Early current flow at +52 mV

no current flows when the membrane is clamped at +52 mV

Calculated ENa in squid neurons

+55 mV

Early current carrier identification

carried by entry of Na+ into the axon because no current flows at ENa

Removing external sodium effect

the early current reversed in polarity becoming an outward current

Removing external sodium effect on ENa

would make ENa negative reversing the electrochemical gradient causing Na+ to flow outward

Reversal of polarity restoration

reversed back to normal when external Na+ was restored

Outward current cause

due to the flux of another ion other than sodium not affected by external sodium removal

Strongest evidence for K+ efflux

amount of K+ efflux from the neuron is correlated with the magnitude of the late outward current

Ionic permeability mechanisms

two different mechanisms suggested because inward current was transient and outward current was sustained

Confirmation of two mechanisms

confirmed by using drugs that block each current separately

Na current blocker

Tetrodotoxin TTX

K current blocker

Tetraethylammonium TEA

Na and K current pathways

use different independent pathways

Ionic current equation

Iion = gion Vm – Eion

Electrochemical driving force

Vm – Eion determines the direction of ionic current and its magnitude

HH conductance calculation

calculated the dependence of Na+ and K+ conductances on time and membrane potential using voltage clamp

Na and K conductances behavior

initially increase in amplitude as Vm is made more positive

K+ driving force direction

positive and outward if Vm is more positive than EK negative and inward if Vm is more negative than EK

Na+ driving force direction

positive and outward if Vm is more positive than ENa meaning electrical force pushing Na+ out is greater than chemical force pushing Na+ in