Excitable Membranes

What is an excitable membrane?

• Any plasma membrane that can hold a charge and propagate electrical signals.

Two types of Excitable Membranes

1. Muscle Cells – excite and then contract.

2. Neurons – transmit electrical impulses

Excitable Membrane Function: Outline

1. Resting Membrane Potential

2. Graded Potentials

3. Action Potentials

Resting Membrane Potential

• All excitable membranes maintain a non-0 resting membrane potential

Neurons = -70 mV

Muscle Cells: -85 mV

Simple DiffusionSimple Diffusion

molecules molecules across across membranesmembranes

Net movement from an area of high concentration to low concentration

Simple diffusion is ONLY ONLY ONLY efficient over short distances!!!!!!!!!!!!!!!!!!!!!

GradientsGradients

e.g. e.g. Pressure, concentration, temperature, energyPressure, concentration, temperature, energy

Molecules move “down” gradients Molecules move “down” gradients from from “Hi” to “Lo”,“Hi” to “Lo”, spontaneously spontaneously

A A GRADIENTGRADIENT is a difference in any parameter over distance is a difference in any parameter over distance

Simple Diffusion Across a MembraneSimple Diffusion Across a Membrane

Outside Inside

Net flux (JNet flux (Jnet net ) occurs from high to low concentration) occurs from high to low concentration

and will continue until concentration gradient disappearsand will continue until concentration gradient disappears

Cell MembraneCell Membrane

CCoo > C > Cii

JJnetnet == P P xx AA xx (Co – Ci)(Co – Ci)

Fick’s First Law of DiffusionFick’s First Law of Diffusion

JJnet net = net = net rate of diffusionrate of diffusion

PP = permeability constant = permeability constantA A = membrane surface area = membrane surface areaCo - CiCo - Ci = concentration gradient= concentration gradient

P and A = biological components!!P and A = biological components!!

PermeabilityPermeabilityAnd And Surface Area Surface Area

varies betweenvaries between 1) cell types 1) cell types 2) organ systems2) organ systems

P and A = biological components!!P and A = biological components!!

PermeabilityPermeabilityAnd And Surface Area Surface Area

varies betweenvaries between 1) cell types 1) cell types 2) organ systems2) organ systems

Systems differ due to differences in Exchange across cell membranes

Cell Membranes are Cell Membranes are selectively permeableselectively permeable

Protein Channel

Transporter Protein

ATP-ase PumpProtein

Neuron Cell Membrane

Small Intestine Cell Membrane

Resting Membrane Potential: Ionic Concentration Gradients

K+

Na+

Cl -

Proteins (-)

Resting Membrane Potential: Membrane Channels

1) LOTS OF K+ Leaks out by Diffusion

2) Na+ cannot leak in

3) Cl– Leaks out electrical repulsion due to Proteins

1

2

3

K+Na+

Cl -

Resting Membrane Potential

1) At rest, K+ leak results in a negative membrane

K+Na+

Cl - Why? Positive Ions moving OUT of a cell result in fewer positive ions inside the cell

This results in a MORE NEGATIVE ICF

0

-100

Vo

ltag

e

Time

2) Chloride leak ensures stabilization of resting potential

Neg. ions moving out make membrane a little more positive

1

2

Resting Membrane Potential: Maintenance of Conc. Gradients

How can a cell maintain [ions] different from diffusion equilibrium?

For resting potentials to be maintained excitable cells must maintain [ions] different from equilibrium

K+Na+

Cl -

Active Transport Active Transport Active Transport Active Transport

The net movement of molecules against a chemical or electrical gradientThe net movement of molecules against a chemical or electrical gradient

Active Transport Active Transport

Net flux (JNet flux (Jnet net ) occurred from low to high concentration) occurred from low to high concentration

Outside InsideCCoo less than C less than Cii

drmunro

Cell MembraneCell Membrane

Active transportActive transport

CoCo ConcConcinsideinside

(mmol/L)(mmol/L)

timetime

Steady StateSteady StateCi = CoCi = Co

jjii = j = jee

jjnetnet = 0 = 0

((requires the use of ATPrequires the use of ATP))

ATP useATP usemaintains the maintains the conc. differenceconc. difference

Na+-K+ ATPase PUMP (Active Transport)

1) ATP binds to PUMP & Na+ enters

2) ATP releases energy which pumps Na+ OUT

3) K+ enters PUMP

4) Return to original shape pumps K+ IN

The pump maintains [Na+] OUT and [K+] IN…….….thus, K+ can leak via channels resulting in a negative resting potential!

Excitement of the Excitable Membrane

• Excitable membranes will deviate from resting potential when a Stimulus is applied

The resulting small amplitude fluctuations are called

Graded Potentials

Stimulus is any external factor that causes a change in membrane voltage

Examples: Electricity Pressure Light

Graded Potentials: Characteristics

1) Can result in hyper-polarization or depolarization

Graded Potentials: Characteristics

2) Amplitude (voltage) is equal to stimulus strength

Stimuli

Membrane Voltage

Graded Potentials: Characteristics

3) Degrade over then length of a membrane

Stimulus applied

Length of Excitable Membrane

Loss of Graded Potential

Graded Potentials: Summation

4) Summation: The closer successive STIMULI, the greater amplitude the graded potential

Action PotentialDefinition: Depolarization of an excitable membrane in response to a threshold stimulus

Sub-threshold stimuli Threshold stimulus

Graded Potentials

Two ways to reach THRESHOLD

1) Single, Large Amplitude Stimulus = directly reach membrane threshold voltage

2) Many subthreshold stimuli close together = SUMMATION of graded potentials

Threshold Voltage

Characteristics of Action Potentials

1) All-or-None: when they happen they are ALWAYS exactly the same

Action Potential: All-or-None Principle

Threshold Stimulus Supra-Threshold Stimulus

ALL: As long as the stimulus is at or above threshold, an action potential will occur and it will always be the same magnitude and duration

The size of the stimulus has no effect on the size of the action potential!

Action Potential: All-or-None Principle

Threshold Stimulus Sub-threshold Stimulus

NONE: If the stimulus is not strong enough to reach threshold voltage, no action potential will occur

Important Note:The all-or-none principle ONLY applies to a particular membrane with certain [ion]

Change the [ion] = change in threshold stimulus,

amplitude of AP, etc.

Action Potential: All-or-None Principle

Characteristics of the Action Potential: 2) 5 stages

(1) Stimulus to Threshold

(2) (3)

(4)

(5) Return to Resting Potential

Action Potential: 1) Stimulus to Threshold

Every stimulus causes some Na+ Channels to OPEN

Resulting in Graded Potentials

[Na+]

[Na+]

Activation gate opens

(1) Stimulus to Threshold

When the stimulus is strong enough, enough Na+ channels open

to bring the membrane to threshold voltage

Action Potential: Ion channels on Plasma Membrane

Na+ and K+ are the VOLTAGE-GATED ION CHANNELS responsible for action potentials

Note: Na+ Voltage-Gated Channels have Activation and Inactivation GATES; K+ only have Activation gates

Action Potential: 2) Depolarization

Once threshold voltage is achieved:

1) ALL activation gates on Na+ Voltage Gated Channels open 2) Na+ RUSHES into Cell

3) Cell Membrane DEPOLARIZES

Action Potential: 3) Repolarization

After a set amount of TIME the INACTIVATION GATE of the Na+ channels CLOSE

This stops Na+ Influx!

Simultaneously, Voltage Gated K+ activation gates OPEN

K+ then leaves the cell by diffusing DOWN its concentration gradient

K+ efflux causes the cell membrane to REPOLARIZE

Action Potential: 4) Hyperpolarization

K+ channels close VERY VERY slowly…..

Thus, a lot of K+ leaves the cell

Membrane potential OVERSHOOOTS

resting to ~ -100 mV

Action Potential: 5) Return to Resting Potential

All activation gates are CLOSED

But, membrane is HYPERPOLARIZED….so how does it reset to -70 mV?But, membrane is HYPERPOLARIZED….so how does it reset to -70 mV?

Na+-K+ ATPase Pump Restores Ion Concentrations….thus, K+ & Cl- can leak……thus membrane re-stabilizes to -70 mV

Characteristics of Action Potentials

1) All-or-None: when they happen they are ALWAYS exactly the same

2) They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential

3) Absolute & Relative Refractory Periods

Action Potential: Refractory Periods

Na+ activation gates open K+ activation gates OPEN

No stimulus can produce 2nd AP

SupraThreshold Stimulus can

produce 2nd AP

Guarantee that each AP can undergo its Depolarization/Repolarization Phase

Characteristics of Action Potentials

1) All-or-None: when they happen they are ALWAYS exactly the same

2) They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential

3) Absolute & Relative Refractory Periods

4) Their strength DOES NOT diminish over distance

Action Potentials: Do not DIMINISHStimulus Applied

Once started, an Action Potential will maintain it strength down the length of a neuron or muscle cell!

Characteristics of Action Potentials

1) All-or-None: when they happen they are ALWAYS exactly the same

2) They consist of 5 stages: 1) Stimulus to Threshold 2) Depolarization 3) Repolarization 4) Hyperpolarization 5) Return to Resting Membrane Potential

3) Absolute & Relative Refractory Periods

4) Their strength DOES NOT diminish over distance

5) Stimulus strength determines the FREQUENCY of Action Potentials

AP are frequency modulated!

Poked with a finger

Low frequency of AP

High frequency of AP

Weak threshold stimulus

Strong threshold stimulus

Abnormal Membrane Potentials

• Hyperkalemia: HIGH K+ in ECF (ISF)

– Consequences: More excitable membranesCELLS ALWAYS IN REFRACTORY PERIOD, Heart stops!

Normokalemia Hyperkalemia

Given during Lethal Injection!

Abnormal Membrane Potentials

• Hypokalemia: low K+ in ECF

– Consequences: Hyperpolarization, less excitable membranes

Muscles & Neurons don’t work

Normokalemia Hypokalemia