Transcript Week2

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 Diffusion
Net movement from an area of high concentration to low concentration
molecules across membranes
Simple diffusion is ONLY ONLY ONLY efficient over short distances!!!!!!!!!!!!!!!!!!!!!
Gradients
A GRADIENT is a difference in any parameter over distance
Molecules move “down” gradients
from “Hi” to “Lo”, spontaneously
e.g.
Pressure, concentration, temperature, energy
Simple Diffusion Across a Membrane
Outside Co > Ci
Inside
Cell Membrane
Net flux (Jnet ) occurs from high to low concentration
and will continue until concentration gradient disappears
Fick’s First Law of Diffusion
Jnet = P x A x (Co – Ci)
Jnet
= net rate of diffusion
P
= permeability constant
A
= membrane surface area
Co - Ci = concentration gradient
P and A = biological components!!
Permeability
And
Surface Area
varies between
1) cell types
2) organ systems
Systems differ due to differences
in Exchange across cell membranes
Transporter
Protein
ATP-ase Pump
Protein
Protein
Channel
Cell Membranes are selectively permeable
Neuron
Cell Membrane
Small Intestine
Cell Membrane
Resting Membrane Potential:
Ionic Concentration Gradients
Na+
Cl -
K+
Proteins (-)
Resting Membrane Potential:
Membrane Channels
1) LOTS OF K+ Leaks out by Diffusion
3
2) Na+ cannot leak in
3) Cl– Leaks out electrical repulsion
due to Proteins
1
2
Na+
Cl -
K+
Resting Membrane Potential
1) At rest, K+ leak results in a
negative membrane
Na+
K+
Cl -
Why? Positive Ions moving OUT of a cell
result in fewer positive ions inside the cell
This results in a MORE NEGATIVE ICF
Voltage
0
1
2
2) Chloride leak ensures stabilization
of resting potential
Neg. ions moving out make
membrane a little more positive
-100
Time
Resting Membrane Potential:
Maintenance of Conc. Gradients
For resting potentials to be maintained
excitable cells must maintain [ions] different from equilibrium
Na+
K+
Cl -
How can a cell maintain [ions] different from diffusion equilibrium?
Active Transport
The net movement of molecules against a chemical or electrical gradient
Active Transport
Outside
Co less than Ci
Inside
Cell Membrane
Net flux (Jnet ) occurred from low to high concentration
drmunro
Active transport
(requires the use of ATP)
Conc
inside
(mmol/L)
Steady State
Ci = Co
ji = je
jnet = 0
Co
time
ATP use
maintains the
conc. 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
Stimulus is any external
factor that causes a change
in membrane voltage
Examples: Electricity
Pressure
Light
The resulting small amplitude
fluctuations are called
Graded Potentials
Graded Potentials: Characteristics
1)
Can result in hyper-polarization or depolarization
Graded Potentials: Characteristics
2)
Amplitude (voltage) is equal to stimulus strength
Membrane
Voltage
Stimuli
Graded Potentials: Characteristics
3)
Degrade over then length of a membrane
Loss of Graded Potential
Length of Excitable Membrane
Graded Potentials: Summation
4) Summation:
The closer successive STIMULI, the greater amplitude the graded potential
Action Potential
Definition: Depolarization of an excitable membrane in response to a threshold stimulus
Graded Potentials
Sub-threshold stimuli
Threshold stimulus
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
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!
Threshold Stimulus
Supra-Threshold Stimulus
Action Potential: All-or-None Principle
NONE: If the stimulus is not strong enough to reach threshold
voltage, no action potential will occur
Threshold Stimulus
Sub-threshold Stimulus
Action Potential: All-or-None Principle
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.
Characteristics of the Action Potential:
2) 5 stages
(2)
(3)
(1) Stimulus to Threshold
(5) Return to Resting Potential
(4)
Action Potential: 1) Stimulus to Threshold
[Na+]
Activation
gate opens
[Na+]
Every stimulus causes some
Na+ Channels to OPEN
Resulting in Graded Potentials
When the stimulus is strong enough,
enough Na+ channels open
to bring the membrane to threshold voltage
(1) Stimulus to Threshold
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
3) Cell Membrane DEPOLARIZES
Once threshold voltage is achieved:
1) ALL activation gates on Na+
2) Na+ RUSHES into Cell
Voltage Gated Channels open
Action Potential: 3) Repolarization
After a set amount of TIME the INACTIVATION GATE of the Na+ channels CLOSE
This stops Na+ Influx!
K+ efflux causes the cell
membrane to
REPOLARIZE
Simultaneously, Voltage Gated K+ activation gates OPEN
K+ then leaves the cell by diffusing DOWN its concentration gradient
Action Potential: 4) Hyperpolarization
Membrane potential
OVERSHOOOTS
resting to ~ -100 mV
K+ channels close VERY VERY slowly…..
Thus, a lot of K+ leaves the cell
Action Potential: 5) Return to Resting Potential
All activation gates are CLOSED
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
SupraThreshold
Stimulus can
produce 2nd AP
Na+ activation gates open
K+ activation gates OPEN
No 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 DIMINISH
Stimulus 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!
Low frequency of AP
Weak threshold stimulus
Poked with a finger
High frequency of AP
Strong threshold stimulus
Abnormal Membrane Potentials
• Hyperkalemia: HIGH K+ in ECF (ISF)
Normokalemia
Hyperkalemia
– Consequences: More excitable membranes
CELLS ALWAYS IN REFRACTORY PERIOD, Heart stops!
Given during Lethal Injection!
Abnormal Membrane Potentials
• Hypokalemia: low K+ in ECF
Normokalemia
Hypokalemia
– Consequences: Hyperpolarization, less excitable membranes
Muscles & Neurons don’t work