Session 1: Cell membrane physiology and cellular communication

Question 1

Classify cell membrane proteins into nine clinically important functional categories.

Answer 1

1. Pumps
2. Channels
3. Receptor proteins
4. Cell adhesion molecules (CAMs)
5. Enzymes
6. Carriers
7. Signal transducers
8. Structural proteins (GPI)
9. Glycoproteins

Question 2

Identify which functional category of cell membrane proteins are involved in intercellular communication.

Answer 2

Enzymes

Question 3

Identify the two principal groups of excitable tissues in the body.

Answer 3

Nerve tissue

Muscle tissue

Question 4

Define cellular membrane potentials and indicate the physiological importance thereof.

Answer 4

Potential differences across cell membranes measured in millivolts.

Physiological importance:

• Generating nerve impulses
• Triggering cell contraction
• Influence secretion in some secretory cells

Question 5

Classify cell membrane potentials into three broad categories and provide general examples of graded potentials.

Answer 5

1. Resting membrane potentials
2. Action potentials
3. Graded potentials
   * Na+/K+ ATPase pump
   * Na+ and K+ leak ion channels (K+ flux 50-100 x that of
   NA+)
   * Large negatively-charged impermeant intracellular
   proteins

Question 6

List the 3 major contributing phenomena regarding the origin of the resting membrane potential (RMP) and briefly describe the mechanism of each phenomenon.

Answer 6

1. Potassium Diffusion
   - We assume that the only movement of ions through the membrane is diffusion of potassium ions, as demonstrated by the open channels between the potassium symbols inside and outside the membrane. Because of the high ratio of potassium inside to outside, the Nernst potential corresponding to this ratio is -94 millivolts. Therefore if potassium ions were the only factor causing the resting potential, the resting potential inside the fiber would be equal to -94 millivolts.
2. Sodium Diffusion
   - The ratio of Na ions from inside to outside the membrane is 0.1, which gives a calculated Nernst potential of +61 millivolts. If the membrane is highly permeable to potassium, but slightly permeable to sodium, the diffusion of potassium contributes far more to the membrane potential than does the diffusion of sodium. In the normal nerve fiber, the permeability of the membrane to K is 100 as great as its permeability to Na, this gives an action potential of -86 millivolts using the Goldman equation. This is near the K+ potential (-90 mv)
3. Na+-K+ Pump
   - Continuous pumping of 3 Na+ to the outside occurs for each 2 K+ pumped to the inside of the membrane, creating an additional an additional degree of negativity on the inside beyond that which can be ac counted for diffusion alone.

• Therefore the net membrane potential when all these contributing factors are operative at the same time is about -90 mV.

Question 7

Make a distinction between RMP-values of large and small nerve and muscle fibres.

Answer 7

Large nerve: -90 mV
Large muscle: -90 mV

Small nerve: -40 to -60 mV
Small muscle: -40 to -60 mV

*The average for both is -70mV

Question 8

Define action potential and and state one synonym for the term.

Answer 8

Definition: Brief, rapid, large changes in membrane potential during which the potential actually reverses so that the so that the inside of the excitable cell transiently becomes more positive than the outside.

Synonym: Impulse

Question 9

Briefly explain the activation and inactivation of the ion channels responsible for the propagation of action potentials in 3 steps.

Answer 9

Step 1:
Membrane is at rest in a polarised state because of the -90mV negative membrane potential.

Step 2:
Initial stimulus leads to opening of sodium channels where Na+ enters axon which leads to membrane depolarisation.

Step 3:
At peak of impulse, membrane becomes highly permeable to sodium ions.
Potassium channels open more than normal and potassium leaves axon to reestablish the normal negative RMP. This is the repolarisation period.

Question 10

Define an afterpotential(after hyperpolarisation) and explain the physiological cause thereof.

Answer 10

Definition: the small action potential generated following termination of the spike or main potential, it has negative or positive phases, the latter being in fact more negative than the resting potential.

Physiological cause: many potassium channels remain temporally open after repolarisation is complete.

Question 11

Explain the causes of the rapid depolarisation, plateau- and rapid depolarisation phases of an action potential in cardiac muscle fibers.

Answer 11

The excited membrane does not repolarise immediately after depolarisation

The reaction occurs in the cardiac muscle fibers where the plateau lasts between 0.2-0.3 s and causes contraction of the cardiac muscle to last for the same period of time. Several factors cause the plateau.

There are 2 types of channels that enter the depolarisation process:
- Type 1:
* voltage activated sodium pumps called “fast channels”
* voltage activated calcium sodium channels called
“slow channels”
(Opening fast channels causes the spike portion of
the action potential where the opening slow channels
are responsible for the plateau portion of the action
potential. The RMP is -80 to -90 mV)

• Type 2:
• voltage gated potassium channels are slower to open often not opening much. This delays the potential membrane to return to its negative value.

Question 12

Name 3 types of impermeable negatively charged ions in cells and briefly state their importance regarding the origin of membrane potentials.

Answer 12

Anions of protein molecules, organic phosphate compounds, and sulphate compounds.

Importance: Responsible for the negative charge inside the fiber when there is a deficit of positively charged K+ ions and other positive ions.
- This is bc these anions cannot leave the interior of the axon so any deficit of the positive ions inside the membrane leaves an excess of these impermeant negative anions.

Question 13

Briefly explain the concept “threshold of an action potential”.

Answer 13

An action potential will not occur until the initial rise in membrane potential is great enough to create the vicious cycle.

Question 14

Describe the physiological mechanisms with regard to the propagation of action potentials, indicate the direction of their propagation and briefly explain the “all-or-nothing” principle of impulse conduction.

Answer 14

Physiological mechanisms:
A nerve fiber gets excited in its midportion and suddenly develops increased permeability to Na+. Current flows from the depolarised areas of the membrane to the adjacent resting membrane areas.

Positive charges are carried by the inward-diffusing sodium ions through the depolarised membrane along the core of the axon.

These positive charges increase the voltage inside the large myelinated fiber to above the threshold voltage value, thus initiating an action potential.

This leads to the opening of the sodium channels and the explosive action potential spreads until the entire fiber length is depolarised. This is called a nerve or muscle impulse.

Direction of the propagation:
The AP has spreads in all directions away from the stimulus until the entire membrane has become depolarised.

All-or-nothing principle:
Once an action potential has been elicited at any point on the membrane, the depolarisation process travels over the entire membrane if conditions are right, but it doesn’t travel at all if conditions are not right.

Question 15

List 3 factors that can initiate an action potential and give examples of each in the body.

Answer 15

1. Mechanical- stretching
2. Electrical- signals between successive muscle and heart cell
3. Chemical- chemical of neurotransmitter of neurons

Question 16

Explain the differences between acute local potential, acute subthreshold potential, latent period, hypopolerisation and hyperpolarisation.

Answer 16

Acute local potential: a weak negative electrical stimulus when increased brings about a point at which excitation takes place. This stimulus disturbs the membrane.

Acute subthreshold potential: when the acute local potential fails to elicit an action potential.

Latent period: A short drop in potential change of the stimuli. A period of time in electrophysiology between the onset of the stimulus and the peak of the action potential.

Action potential: stimuli required to surpass the threshold.

Hypopolerisation: Lowering of the voltage difference across the membrane.

Hyperpolarisation: Heightening of the voltage difference across the membrane.

Threshold level= 65 mV

Question 17

Distinguish by referring to the definitions and mechanisms, between the absolute refractory and relative refractory periods.

Answer 17

Absolute refractory period: the period during which a second action potential cannot be elicited, even with a strong stimulus.

Relative refractory period: the period when a stronger than normal stimulus elicits an action potential.

Question 18

Explain the concept “saltatory conduction”.

Answer 18

The action potential that is conducted from node to node (rather than progressively) down a nerve fiber. Electrical current flows through the surrounding ECF outside the myelin sheath as well as inside the axon exiting each successive nodes after one after the other. Thus, the nerve impulse jumps down the fiber.

Question 19

Identify sites where saltatory conduction occurs.

Answer 19

The Nodes of Ranvier of a nerve fiber

Question 20

Indicate where the slowest and most rapid nerve impulse conduction occurs.

Answer 20

Slowest: Myelin sheaths
Rapid: The Nodes of Ranvier (as they are unmyelinated and myelin sheath acts as an insulator)

Question 21

Discuss how extracellular calcium ion concentrations influence membrane excitability.

Answer 21

The [ ] of Ca ions in the ECF has a large effect on the voltage level at which the sodium channels become opened by a small increase in the membrane potential from its normal, negative level. Therefore the cell membrane becomes highly excitable, sometimes discharging repetitively w/o provocation rather than remaining in the resting state.

Question 22

Identify 3 tissues that exhibit self-induced discharges (rhythmicity/spontaneous action potentials) and the physiological importance of this rhythmicity.

Answer 22

1. Heart - rhythmical beat of the heart
2. Smooth muscle - rhythmical peristalsis of the intestines
3. Nerves of the CNS - neuronal events such as the rhythmical control of breathing

Question 23

Explain how spontaneous rhythmicity occurs in excitable tissue.

Answer 23

For spontaneous rhythmicity to occur, the membrane must be permeable enough to Na ions( or both the Na and Ca ions through the calcium sodium channels) to allow automatic membrane depolarisation.

The RMP in the rhythmical control centre of the heart is only -60 to -70mV, which is not enough negative voltage to keep the sodium and calcium channels completely closed.

Therefore the following sequence occurs:

1. Some Na and Ca ions flow inward
2. This increases the membrane voltage in the + direction, which further increases the membrane permeability
3. More ions flow inward
4. The permeability increases more, until the action potential is generated. Then at the end of the action potential, the membrane polarises. After another delay of a few milliseconds, spontaneous excitability cause depolarisation again, creating a new spontaneous action potential.

This cycle causes self-induced rhythmical excitation of the excitable tissue.

Question 24

Explain the delay between successive action potentials.

Answer 24

-Towards the end of the of each AP, and for a short
time thereafter, the membrane becomes excessively
permeable to K+ ions.

• This excessive outflow of K+ ions carries a huge
  number of positive charges to the outside of the
  membrane, leaving the inside more negatively
  charged than normal.
• This continues for almost a second after the preceding
  action potential is over, thus drawing the membrane
  potential nearer to a state of hyperpolarisation.
• As long as this hyperpolarisation state exists, self-
  excitation of the cell will not occur. But, the state of
  hyperpolarisation gradually disappears, thereby
  allowing the membrane potential again to increase up
  to the threshold for excitation. Suddenly, a new action
  potential results. This process is continuously repeated.

Question 25

Discuss the structure of Na+/K+ ATPase pump.

Answer 25

• It is responsible for maintaining the high K+ and low
  Na+ [ ] in the ICF
• It is an electrogenic pump with a coupling ratio of 3:2
• It moves 3 positive charges out of the cell for each 2
  that move in
• Found in all parts of the body and its activity is
  inhibited by the digitalis glycosides that are used to
  treat cardiac failure
• A heterodimer made up of 2 alpha sub-units w/ a
  molecular weight of appr. 100 000 each and 2 beta
  sub-units w/ a molecular weight of 55 000 each
• Both sub-units extend through the cell membrane
  (their separation would eliminate activity)
• The beta sub-unit is a glycoprotein, whereas the Na+
  and K+ transport occur through the alpha sub-unit
• The alpha sub-unit has ATPase activity and
  intracellular Na+ and ATP-binding sites
• And an intracellular phosphorylation site and has
  extracellular binding sites for K+ and ouabain

Question 26

Briefly describe 3 important functions of the Na+/K+ ATPase pump.

Answer 26

1. Responsible for maintaining high K+ and low Na+ [ ] in
   the ICF
2. Maintains the normal RMP (so that nerve impulse
   conduction is possible)
3. Maintains cell volume and prevents cell lysis

Question 27

Explain the role of the Na+/K+ ATPase pump regarding action potentials.

Answer 27

• The membrane potential is determined by the
  distribution of ions across the cell membrane and the
  nature of the cell membrane.
• The concentration gradient for K+ facilitates the
  movement of K+ out of the cell via K+ channels, but
  the electrical gradient therefore is in the opp. (inward)
  direction.
• Consequently, an equilibrium is reached in which the
  tendency for K+ to move out of the cell is balanced by
  its tendency to move into the cell.
• At this equilibrium, there is a slight cation excess on
  the outside and a slight anion excess on the inside.
• This condition is maintained by the Na+/K+ ATPase
  pump, which is electrogenic, because it pumps 3 Na+
  out of the cell for every 2 K+ that it pumps into the cell.
• This pump therefore contributes a small amount to the membrane potential itself. The number of ions
  responsible for the membrane potential is a minute
  fraction of the total number of ions present and the
  total [ ] of the + and - ions are equal everywhere,
  except along the membrane.
• Na+ influx doesn’t compensate for K+ efflux, bc the
  K+ channels make the membrane more permeable to
  K+ than Na+

Question 28

Name two other primary active transport pumps, besides the Na+/K+ ATPase pump, and state one location for each pump.

Answer 28

1. Mg++/Ca++ ATPase pump: In the sarcoplasmic reticulum of muscle cells, that keeps the cytosolic [Ca++] under 0.1 micromole/L
2. Potassium-hydrogen ion (K+/H+): In the gastric
   mucosa , that controls the H+ secretion in the stomach
   during digestive processes.