PLASMA MEMBRANE AND MEMBRANE POTENTIAL IN THE NERVE CELL

TABLE OF CONTENTS

Updated: Jan. 24, 2008

LECTURE INFORMATION

KEY CONCEPTS IN THIS LECTURE

1. The plasma membrane of a nerve cell functions as a barrier between the cytoplasm and the extracellular environment of the cell. The "fluid mosaic model" of the membrane states a membrane consists of a lipid bilayer in which a number of functional proteins and other inclusions, such as glycoproteins, are embedded. Membrane proteins in a nerve cell have a number of specific functions, such as permitting selective passive of an ion (=ion channel), moving an ion against a concentration gradient (=ion pump), or acting as a receptor which communicates information about events in the immediate environment.

2. Communication between cells (e.g., via a neurotransmitter or hormone) can elicit a response within a cell if a receptor is present. The ligand (e.g., neurotransmitter or hormone) and receptor form a "lock and key" complex which activates a cascade of events leading to an intracellular response. This cascade is amplified and often involves a number of proteins embedded in the membrane (e.g., adenylyl cyclase) and present in the cytoplasm (e.g., protein kinase). There are a number of different pathways by which a ligand can generate a specific intracellular event.

3. A solution is composed of solute and solvent (water). Membrane transport of solute (such as glucose or Na+) is by either diffusion (passive, down a concentration gradient), facilitated diffusion (passive, mediated, down a concentration gradient, or active transport (requiring energy, mediated, but movement against a concentration gradient).

4. Ion distribution across the plasma membrane is based largely on physical laws involving ion charge and concentration. The distribution of an ion across the membrane in a resting neuron can be determined by the Nernst equation and a modified Nernst, called the Goldman equation. The resting nerve has mostly Na+ on the outside of the membrane and K+ and - charged, nondiffusible protein on the inside. Because there is a little leakage of K+ to the outside (K+ is more permeable than Na+), the net membrane charge is positive on the outside and negative on the inside. This resting, or non-firing, nerve has a resting of about -70 mv.

LECTURE OUTLINE

I. STRUCTURE OF THE PLASMA MEMBRANE

A. Plasma membrane--the barrier between what goes on in the cytoplasm
and the cell's immediate environment
1. Plasma membrane is selectively permeable

B. Structure of Plasma Membrane
1. Most of the plasma membrane contains phospholipids in a lipid bilayer
a. The polar ends are hydrophilic (=dissolve in water easily) while the
fatty acid tails are hydrophobic (=dissolve in water with difficulty).
2. Plasma membrane is more structurally complex than a lipid bilayer.
a. Numerous proteins are imbedded in the lipid bilayer that have
many different functions.
1) act as ion channels, as in nerve function
2) act as a receptor for a hormone/neurotransmitter
3) are carrier molecules for specific substances
4) docking proteins for vesicle identification
5) glycoproteins are markers for cell-cell identification.
3. Cholesterol embedded in the membrane provides membrane fluidity

II. MEMBRANE TRANSPORT

Plasma membrane is selectively permeable.

A. SOLUTE FLOW--Physical principles governing movement of solutes.
1. Diffusion--the passive movement of particles down a concentration
gradient until an equilibrium is achieved.
a. Factors influencing the rate of diffusion.
1) Concentration gradient--increased rate
2) Membrane permeability--increased rate
3) Increased surface area--increased rate
4) Increased molecular weight--decreased rate
5) Increased thickness of membrane--decreased rate
b. These effects are summarized by Fick's Law of Diffusion
1) Importance of diffusion coeficients (e.g. K+ > Na+)
2. Facilitated Diffusion - Some solutes (especially ions) move
across a membrane more rapidly than predicted from passive
diffusion.
a. Characteristics of Carrier-mediated transport
1) Saturation of carrier limits solute transport
2) Specificity for a solute
3) Competition can occur between closely related solutes
4) Competition follows the Law of Mass Action
b. Example of facilitated diffusion: Glucose transport into the nerve
3. Active Transport. A carrier molecule is involved, but solute movement
is against a concentration gradient
a. energy is expended
1) Structural and biochemical characteristics of the ATPase pump
2) Example: Active Transport of Na+ and K+ in the nerve (Animation)

III. MEMBRANE POTENTIAL

Established that net diffusion across a semi-permeable membrane occurs
down a concentration gradient.

A. But this principle becomes more complex when you consider ions
(=charged particles) because ions are influenced by both 1) an
electrical gradient and 2) a concentration gradient.

B. An abundance of anions (=large, impermeable proteins) on cytoplasmic side
results in a charge asymmetry
1. K+ is much more permeable than Na+ so it is mostly found inside the cell
a. Remember that like charges (+&+) repel; opposite charges (+&-) attract
2. Both electrical & concentration gradients influence ion distribution (e.g. K+)
a. These forces often work in opposition (as in the case of K+)

C. Charge across the membrane results. Slightly positive outside and
negative inside--the result is a resting membrane potential

IV. ELECTROCHEMICAL BASIS FOR RESTING MEMBRANE POTENTIAL

A. Three ions are usually involved in establishing a membrane potential:
1. Distribution of Na+, K+, Anions (=protein) across membrane
2. What determines that the ion distribution should be as such?
a. Na+/K+ pump, but it is not that important
b. Recall that the concentration gradient can oppose the electrical
gradient for an ion, but an equilibrium is reached
c. Equilibrium Potential (E) and the Nernst Equation
1) Limitations of Nernst Equation
d. Goldman Equation considers differences in diffusion rate and
better approximates resting potential
e. Summary of resting potential (Animation)
Note: 3Na+/2K+ ATPase pump is not a major player here
B. What is the relationship of membrane potential to action potential?

STUDY QUESTIONS

Describe the fluid mosaic model of membrane structure.
Various proteins are embedded in the plasma membrane of a neuron. List some functions of these proteins.
What is it about the target cells for a neurohormone that permit them to respond while other non-target cells exposed to the same neurohormone completely ignore its presence?
The same neurotransmitter might stimulate some neurons while inhibiting others. What is it about the target neuron which makes these different responses possible?
What is Fick's law of diffusion? Which factors influence the rate of diffusion across a membrane? Give examples of how membranes might be altered in a biological system to change the rate of diffusion (Consider different ions).
Compare and contrast the 'second messenger" pathways with other signal transduction mechanisms (see Figures 2-34, 2-35 in Carlson).
Compare and contrast the major avenues of water transport across the plasma membrane. How are solutes transported across the plasma membrane? Compare and contrast the functional characteristics of each transport mechanism. Give examples of how these mechanisms are important for nerve function.
Define and give the physiological significance (how or why it is important) for the following terms:
- amplication of a signal
- G protein (inhibitory or stimulatory)
- coupled reaction
- ATP
- electron transport system (ETS)
- lactic acid
In carrier-mediated transport of Solute Q, there is always the possibility that a similarly-shaped molecule might compete for the transport protein (that is, act as an antagonist to transport of the Solute Q). Graph the rate of Solute Q transport (Y axis) against increasing Solute Q concentration (X axis) in the 1) presence and 2) absence of an antagonist. Explain. Would you expect to find a similar effect in other systems which employ this "lock and key" interaction (e.g., between a substrate and its enzyme or a neurotransmitter and its receptor)?
Because of its charge, glucose normally diffuses through the plasma membrane slowly. However, facilitated diffusion of glucose occurs more rapidly as long as the carrier molecules are not saturated. Given Fick's Law of Diffusion, which parameter(s) must change to permit this more rapid diffusion in the presence of a carrier. Explain.
Which ions (Na+, K+, Cl-, protein-) have a high concentration outside the neuron and which have a high concentration inside the neuron?
In a resting nerve, why is K+ inside the nerve membrane and Na+ outside rather than vice versa? Explain.
Neurons are only slightly permeable to sodium ions. In which direction is the concentration gradient for sodium? Why? In which direction is the electrical force for sodium? Why?
Does the Na+/K+ ATPase pump move sodium and potassium with or against their concentration gradient? What provides the energy to operate the pump? Describe the sequence of events which results in the transport of 3Na+ and 2K+ (see animation)
What does the term "resting membrane potential" in a neuron mean? What is a typical value for the resting membrane potential? How important is the Na+/K+ ATPase at determined membrane potential? How would ion manipulations (e.g., increasing the external concentration of K+) alter the resting membrane potential?
Review the Nernst and Goldman equations. How are the Nernst equation and Goldman equation applied to understanding membrane potential? Why does the Goldman equation more closely reflect what is actually happening?
Since your text does not the fully discuss neuronal electrical properties, read more about this topic at the following website: Electrical properties of the resting neuron. Consider the following: The squid giant neuron has a much higher ion concentrations than the cat motor neuron, yet the resting potential in both neurons is similar (-70 mV). What does that tell you about absolute ion concentration in determining resting potential?
Thought Question. Some textbooks state that the resting potential for a motor neuron is -60 mV which differs from what Carlson states (-70 mV). Although this difference is slight, can you explain the basis for the discrepency between these values? Remember that not all neuron and muscle cells have exactly the same resting potential. In general, what ionic or membrane factors could explain differences in resting potential? Give examples to prove your point.
Thought Question. Determine the Equilibrium Potential (E) for Ca++. Use the following concentrations: Extracellular = 0.4 mM/l and intracellular = 10 mM/l. The valence (Z) for Ca++ is 2, not 1, as in the case of Na+ and K+. How does a change in valence affect the calculation of E? Given your calculation, how would Ca++ behave if the Calcium gates in a motor neuron opened? What would happen to the resting potential? Explain your reasoning.
Thought Question. When you add ouabain to a nerve preparation, you block the 3Na+/2K+ ATPase pump (at the K+ binding site). The membrane potential is maintained following such treatment, although it does drift slightly from -70 mV. Which direction would it drift (less or greater than -70 mV)? Defend you choice. [Hint: Concentrate on what should happen over time to Na+ flux across the membrane when ouabain is present]
Thought Question. If a neurotransmitter acted to open Choride (Cl-) channels, would the resting potential of a motor neuron depolarize, hyperpolarize, or not change much? Explain you reasoning.
A single neurotransmitter can stimulate one cell type while inhibiting another. Explain how a single neurotransmitter can act so differently. Defend your answer with specific examples.

ADDITIONAL INFORMATION ON THE INTERNET

Osmosis. A description of osmosis from Colorado State. Also, a Simulation for Hydrostatic Pressure

Membrane Architecture. Description for a number of membrane structural components and what they do.

Membrane Transport. A slide show on membrane structure and transport from the University of Tampa.

Membrane Potential. Nicely explained with plenty of figures.

Animations on various Passive and Active Transport Mechanisms across the cell membrane.

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