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What is a Membrane Potential

  • All cells have an electrical potential (voltage) difference across their plasma membrane.
  • Changes in this membrane potential underlie the basis of signal transmission in the nervous system as well as in many other types of cells (including muscle and heart)


How do you measure a Membrane Potential?

  • Membrane potentials can be measured using a very fine micropipette - a microelectrode - that will penetrate the cell membrane. The other electrode is placed in the extracellular medium.
  • When the microelectrode impales the cell membrane, the membrane potential goes negative.
  • Membrane potentials are always expressed as the potential inside the cell relative to the extracellular solution


Give some examples of resting mmbrane potentials

  • Animal cells have negative restin membrane potentials that range from -20mV to -90mV
  • Cardiac and skeletal muscle cells have the largest resting membane potentials: -80 - -90mV
  • Nerve cells have resting potentials in the range -50 to -70mV
  • Smooth muscle cells have resting potentials in the range -50 to -75mV
  • Standard nerve cells = -70mV


Describe the selective permeability of the phospholipid bilayer

  • Hydrophobic interior so it is permeable to small uncharged molecules (O2, C02, H2O and ethanol) but very impermeable to charged molecules (ions)
  • Ion channels are proteins that enable ions to cross the cell membrane as they have an aqueous pore though which ions flow by diffusion



How is a membrane potential set up?

  • The membrane is selectively permeable to different ions (depending on what channels are open)
  • The permeability occurs by way of channel proteins (membrane spanning transport proteins that allow ions to penetrate).
  • Ion channels are characterised by:
  • Selectivity: one (e.g. selective for Na+, K+, Ca2+, Cl-) or a few ion species (non-selective cation permeabiity)
  • Gating: the  channel can be open or closed by a conformational change in the protein molecule.
  • A rapid high rate flow of ions that is always down the electrochemical gradient for the ion
  • Passive


Describe the ionic concentrations for a typical mammalian cell


How is a Resting Membrane Potential Set Up?

  • At rest the membrane has open K+ channels which dominate ionic permeability (for most cells) so is selectively permeable to K+. K+ wll begin to diffuse out of the cell down its concentration gradient.
  • Since anions cannot follow, the cell will become negatively charged inside.
  • The membrane potential will oppose the outward movement of K+ ions and the system will come into equilibrium when the chemical (diffusion) gradient for K+ and the electrical gradent for K+ are equal and opposite.
  • There will be no net movement of K+ but there will be a negative membrae potential.
  • Thus the resting membrane arises becaue the membrane is selectively permeable to K+ ions.


What is the Equilibrium Potential?

The membrane potential at which there is no net movement of the ion across the membrane (Concentration gradient = electrical gradient)


What is the Nernst Equation?

Can be used to calculate the Equilibrium Potential, given the extracellular and intracellular ion concentrations.

(at 37 oC)

Z = Valency so will be 1 for K+ but 2 for Ca2+


Is the real cell perfectly selective to K+?


The real cell is not perfectly selectively permeable to K+ alone so its membrane potential will not be at E(K) (-90mV)

The Na+ and Ca2+ are voltage gated ion channels, normally closed at rest but occasionally flicker and allow  little influx of Na+ and Ca2+ ions raising the resting membrane potential to -70mV - less negative. This is because of IMPERFECT PROTEIN CONFORMATION

The dependence of resting potential on K+ permeability means that changing the E(K) wll change the membrane resting potential. Increasing extacellular [K+] makes E(K) more positive so changes the membrane potential in the same direction.


Describe the resting membrane potentials of cells with LOWER resting potentials

  • Lower selectivity for K+
  • Increased contribution from other channels
  • Smooth muscle cells: ~-50mV


Describe the resting membane potential of skeletal muscle cells

  • Many Cl- and K+ channels open in the resting membrane
  • Resting potential = ~-90mV. Close to both E(Cl) and E(K)


What forms of signalling between and within cells do changes in membrane potentials underlie?

Examples include:

  • Action potential in nerve and muscle cells.
  • Triggering and control of muscle contraction
  • Control of secretion of hormones and neurotransmitters
  • Transduction of sensory information into electrical activity by receptors
  • Postsynaptic actions of fast synaptic transmitters


What does depolarization mean?

A decrease in the size of the membrane potential from its normal value.

Cell interior beomes less negative (NOT NECESSARILY POSITIVE, not necessarily an action potential)

.E.g. a change from -70mV to -50mV

Opening Na+ or Ca2+ ion channels will cause depolarization


What does hyperpolarization mean?

  • An increase in the size of the membrane potential from its normal value.
  • Cell interior becomes more negative
  • E.g.  change from -70mV to -90mV
  • Opening K+ or Cl- channels will cause Hyperpolarization


How can you change membrane ion permeability?

  • In reality, cells have channels open for more than one type of ion. The contribution of each ion to the membrane potential will depend on how permeable the membrane is to that ion.
  • Thus changes in the cell’s permeability to a single ion can change its membrane potential. 
  • Increasing membrane permeability to a particular ion moves the membrane potential towards the Equilibrium potential for that ion



What is the Goldman-Hodgkin-Katz Equation?

Theoretical treatment that fits real membranes quite well


Explain about the selectivity of Nicotinic Acetylcholine Receptors

  • Some channels are less selective e.g. at the neuromuscular junction, motor neurone terminals release ACh which binds to nicotinic acetylcholine receptors on the muscle membrane.
  1. Intrinsic ion channel
  2. Opened by binding of ACh
  3. Channel lets Na+ and K+ through but not anions
  4. Moves the membrane potentail towards 0mV - intermediate between E(Na) and E(K)


How do you control channel activity? What are the types of Gating?

the number of open channels of different types underlies the overall selectivity of the cell membrane.

  • Channel opening is in turn controlled by the gating mechanism that open or close the channels involved.
  • Types of Gating: Ligand, Voltage, Mechanical


Explain about Ligand Gating

  • The channel opens or closes in response to binding of a chemical ligand.
  • E.g. Channels at synapses that respond to extracellular transmitters or channels that respond to intracellular messengers.


Explan about Voltage Gating

  • Channels open or close in response to extracellular transmitters
  • E.g. channels involved in action potentials


Explain about Mechanical Gating

  • Channel opens or closes in response to membrane deformation
  • E.g. channels involved in mechanoreceptors: carotid sinus stretch receptors (channels sense stretch in issue and open according to that stretch), hair cells


What happens at a synapse and where do they occur?

At a synapse, a chemical transmitter released from the presynaptc cell binds to receptors  on the post-synaptic membrane. Synaptic connections occur between:

  • Nerve cell - nerve cell
  • Nerve cell - muscle cell
  • Nerve cell - gland cell
  • Sensory cell - nerve cell


What is a Fast Synaptic Transmission

  • The receptor protein is also an ion channel
  • Transmitter binding causes the channel to open.
  • The transmitter itself causes the channel to open


What happens in an Excitatory Transmission?

  • Excitatory transmitters open ligand-gated ion channel that cause membrane depolarisation; depolarising transmitters open channels wth positive reversal potentials.
  • Channels are selective for Na+, Ca2+ and some cations (nAChR)
  • These transmitters lead to excitation of cells and the change in membrane potential they cause is called an Excitatory Postsynaptic Potental (EPSP
  • An EPSP is not an action potential  - it is a smaller event
  • EPSP may reach different levels depending on amount of transmitter - Graded with the amount of transmitter
  • Longer time cause than an AP
  • Transmitters including ACh and Glutamate


Describe an Inhibitory Synapse

  • Inhibitory transmitters open ligand-gated channels that cause hyperpolarization - open channels selective for K+ or Cl-
  • These transmitters lead to inhibition and the change in membrane potential they cause is called an Inhibitory Postsynaptc Potential (IPSP)
  • The cell is less excitable
  • Transmitters include GABA (gamma-aminobutyric acid), Glycine 


Explain about a Slow Synaptic Transmission (general)

  • The receptor and the channel are separate proteins
  • The receptor has to signal to the channel in one of two basic ways:
  1. Direct G-Protein Gating
  2. Gating via an Intracellular Messenge
  • Both involve a GTP-binding protein


Describe Direct G-Protein Gating

  • G-Potein diffuses through G-Protein Couled receptor (a 7 transmembrane domain protein) to channel
  • It is small as it is one signal to one channel but quite rapid (tends to happen at synapses)


Describe Gating Via An Intracellular Messenger

  • This transmission can take place throughout cell so can interact with distal channels as it allows diffusion throughout cell
  • Amplification by cascade means the transmission lasts longer but it is slower
  • Transmitter binding at the G Protein Coupled Receptor causes the G-protein to diffuse and bind to the enzyme which initiates a signalling cause resulting in an intracellular messenger or Protein Kinase changing the activity of the channel.


What other two factors influence membrane potential?

1. Changes in ion concentation: especially {K+] (~4.5mM). E.g. If the extracellular [K+] is increased, the driving force for membrane potential is reduced so membrane potential sets somewhere else (more depolarised) and therefore more excitable because it is closer to the threshold for action potential generation.

2. Electrogenic pumps: e.g. Sodium pump (1 +ve charge is moved out for each cycle so in some cells, this contributes a few mV directly to the membrane potental, making it more negative. Indirectly, active transport of ions is responsible for the entire membrane potential because it sets up and maintains the ionic gradients.

Sodium-Calcium Exchanger will have a little depolarizing effect on the membrane.