Cell Membrane Transport III - Electrical properties of the cell membrane

Question 1

Learning outcomes

Answer 1

• Explain the ionic basis of membrane potentials
• Understand the principle of the Nernst equation and electrochemical
  equilibrium
• Understand the principle of the Goldman equation and how it relates to
  the steady state membrane potential
• Describe & explain the ionic basis of electrical signalling in excitable
  cells
• Understand that the electrical response of ‘excitable cells’ depends on
  the type of membrane transport processes present in those cells

Question 2

Further Reading (not essential)

Answer 2

Alberts et al. Molecular Biology of the Cell, chapter 11
Alberts et al. Essential Cell Biology, chapter 12

Answer 3

Question 3

Electrical properties of the membrane
are important for cells

Answer 3

• Membrane potential (charge of the membrane) is a major force acting on ions and
  molecules in all cells
• Membrane potential of cells is generally around -70 mV (can vary depending on
  cell type).
• Ions are the most abundant dissolved solutes
• Electrical properties of membranes are important in:
• Muscle contraction, sensory signalling, CNS
• Fluid flows in specialized epithelia
• Intracellular enzyme cascades
• Gene expression, cell growth, cell death
• Gating of channels
• Venus fly traps????

Question 4

Diffusion of ions is determined by:

Answer 4

Membrane permeability, concentration gradient and
voltage gradient

MCV

Question 5

How do we generate a resting
membrane potential?

Answer 5

Question 6

How do we generate a resting
membrane potential?

Answer 6

1. Neutral membrane
   impermeable to ions
2. But… membranes express
   specific ion channels which
   means selective
   permeability of ions

Question 6

How do we generate a resting
membrane potential?

Question 6

How do we generate a resting
membrane potential?

Question 6

How do we generate a resting
membrane potential?

Question 7

A small number of charges
generate a large voltage

Answer 7

Question 8

Ion channel involvement in
membrane potential

Answer 8

• Many ion channels are involved in
  maintenance of membrane potential, K+
  channel is a major one
• Continued efflux of K+ builds up an excess
  of positive charge outside of the cell and
  excess of negative charge on inside of cell
• Build-up of charge impedes further efflux of
  K+
  . Eventually a steady state is reached –
  electrical and chemical driving forces
  are equal and opposite
• Electrochemical gradient: net driving force
  tending to move an ion across a membrane
  is the sum of the concentration and
  electrical gradients

Question 8

Ion channel involvement in
membrane potential

Answer 8

Question 9

Nernst equation – for a single ion

Answer 9

Question 9

Goldman equation – multiple ions
with varying permeabilities

Answer 9

• Cells have many different ion channels in their membranes
• Multiple ion gradients
• At a typical resting potential, the membrane is highly permeable to potassium
  but less so to sodium and/or chloride
• Allows determination of the membrane potential at steady state
• Membrane are permeable to more than one ion meaning a steady state rather
  than equilibrium

Question 9

Nernst equation – for a single ion

Answer 9

• Nernst equation gives the membrane
  voltage which a single ion would be at
  equilibrium
• Considers the electrical gradient and
  chemical gradient for a single ion
• For K+
  : Vm = -60 log10 (140/5) = -86.8 mV
• But we have other ions with varying
  membrane permeabilities!

Question 9

Goldman equation – multiple ions
with varying permeabilities

Answer 9

Question 10

Cells are in a steady state rather
than equilibrium

Answer 10

Question 11

Cells are in a steady state rather
than equilibrium

Answer 11

Passive fluxes of Na+ into and K+ out of the cell are balanced by active
transport in the opposite direction by ATP-dependent Na+
-K+ pump

Question 12

Utilization of electrical properties of
membranes for neuronal signaling

Answer 12

Question 13

Utilization of electrical properties of
membranes for neuronal signaling

Answer 13

Resting membrane potential = ~ -60-70 mV. In nerve cells, membrane potential can be
quickly altered by changes in permeability to certain ions = action potential
Functional significance of action potentials:
* Fast signal transmission over long distances in the nervous system
* Control of hormone release from neuroendocrine and other cells
* Control of muscle contraction
* Coding of sensory stimulus features

Question 14

Voltage-gated cation channels generate
action potentials in electrically excitable cells

Answer 14

• A single polypeptide chain with 4 homologous domains
• Green α helices form central ion conducting pore
• Dark green = selectivity filter
• Red S4 α helices form voltage sensor
• Green triangle forms inactivation gate that obstructs the
  pore in the channel’s inactivated state

Question 15

Voltage-gated cation channels generate
action potentials in electrically excitable cells

Answer 15

Question 15

Voltage-gated cation channels generate
action potentials in electrically excitable cells

Answer 15

Answer 16

Question 17

Voltage-gated Na+ channels can be in 1
of 3 states: Closed, open or inactivated

Answer 17

Action potentials caused by opening and
subsequent inactivation of voltage-gated
Na+ channels.
* Closed when membrane potential is at
the resting membrane potential
* Open when membrane potential
increases past a threshold
* Inactivated is a transient blocking of the
channel (separate from the closed state)
The membrane cannot fire a second
action potential until the Na+ channels
have returned from the inactivated to the
closed conformation

Question 17

How do action potentials work at the
ion channel level?

Answer 17

Change in membrane potential
opens voltage gated Na+
channels, suddenly increasing
membrane permeability to Na+
,
Na+ influx caused depolarization
(increased membrane potential)
Na+ channels close as voltage
gated K+ channels begin to open
Membrane now much more
permeable to K+
, K+ efflux leads
to repolarization (decreased
membrane potential). Na+
-K+
pump also involved.

Answer 18

Question 19

How do action potentials work at the
ion channel level?

Answer 19

Question 19

Action potential are propagated over
long distances

Answer 19

Question 20

Action potential are propagated over
long distances

Answer 20

Multiple dendrites and cell body
receive signals from axons of
other neurons
Single axon can conduct action
potentials over long distances
The axon terminals end on the
dendrites or cell body of other
neurons or on other cell types,
such as muscle or glandular cells

Question 21

Propagation of an action potential
along an axon

Answer 21

AP is the same amplitude along the
length of the axon
AP continues in the same direction, ‘flow
back’ prevented by Na+ channel
inactivation

Question 22

Propagation of an action potential
along an axon

Answer 22

Question 23

Propagation of an action potential
along an axon

Answer 23

Question 24

Myelination increases speed & efficiency
of action potential propagation in nerves

Answer 24

Schwan cells wrap around the axon to
form a myelin sheath
Insulates axonal membrane to reduce
current leak
Myelin sheath is interrupted by nodes of
Ranvier, highly concentrated Na+ and K+
channels
Action potential propagates along a
myelinated axon by jumping from node to
node = saltatory conduction
* Greatly increases conduction velocity
* Greatly reduces energy consumption
(less Na+
-K+ pump activity)

Question 25

Myelination increases speed & efficiency
of action potential propagation in nerves

Answer 25

Question 26

Action potentials cause release of
neurotransmitters at synaptic terminals

Answer 26

Action potentials reaches nerve
terminal and triggers release of
neurotransmitter into synaptic cleft
Neurotransmitter binds to and opens
the chemically-gated ion channels on
the postsynaptic cell
The resulting ion flows alter the
membrane potential of the
postsynaptic cell, thereby transmitting
the signal from the presynaptic to
postsynaptic cell

Question 27

Action potentials cause release of
neurotransmitters at synaptic terminals

Answer 27

Question 28

Summary

Answer 28

• Selectively permeable membranes can produce charge separation
• Very few ions move to generate resting potential
• Nernst equation gives the equilibrium potential if the membrane is only permeable to one
  ion.
• Resting membrane potential dominated by K+ permeability.
• Membrane are permeable to more than one ion meaning a steady state rather than
  equilibrium
• Goldman equation describes the membrane potential for multiple ions with differing
  permeability.
• Action potential is caused by the voltage activation of Na+ and K+ channels (and consequent
  changes in membrane permeability).
• Action potentials are propagated over long distances to cause release of neurotransmitters
  and conduction velocity is increased by myelination and saltatory conduction