Communication & control

The cell membrane & cell excitability

Lecture 3 Marieb & Hoehn (2009) Ch 3 & Ch 11 Sherwood (2009) Ch 3

Lecture Objectives
by the end of the lecture you should be able to
1. 2. 3. 4. 5. 6. 7. List the functions of proteins in the plasma membrane Describe the process of facilitated diffusion & active transport using specific examples Describe the process of exocytosis & endocytosis using specific examples Define resting membrane potential (RMP) & give a typical value using the appropriate units Explain the 3 reasons why a separation of charge exists across the cell membrane Calculate the equilibrium potential for Na+, K+ & ClDescribe how the movement of K+, Na+ & the NaK ATPase pump contribute to the RMP

Plasma Membrane Structure

Fluid lipid bilayer embedded with proteins

Construction of a cell membrane - http://www.wisc-online.com/objects/index.asp?objID=AP1101

Plasma Membrane Structure

Phospholipids Polar end is hydrophilic; nonpolar end is hydrophobic Carbohydrates Small amount on outer surface only Cholesterol Contributes to fluidity & stability of cell membrane Proteins Attached to or inserted within lipid bilayer Functions of membrane proteins
Form water-filled channels across lipid bilayer Serve as carrier molecules Serve as docking-marker acceptors Membrane-bound enzymes Receptor sites Cell adhesion molecules (CAMs) Proteins on surface are important in cells ability to recognize self & in cell-to-cell interaction

Membrane Transport
Cell membrane is selectively permeable Two properties influence whether substances can permeate the cell membrane without assistance Relative solubility of the particle in lipid Size of the particle

Membrane Transport
Unassisted membrane transport, i.e. molecules can penetrate through the plasma membrane on their own Diffusion Osmosis
Assisted membrane transport or carrier-mediated transport Facilitated transport Active transport Vesicular transport

Diffusion
Uniform spreading of molecules due to their random motion

They move from area of high concentration to area of low concentration

Ions are influenced by concentration & charge, hence they move down the concentration & electrical gradient, called an electrochemical gradient Process is crucial to survival of every cell
Plays important role in
Exchange of O2 & CO2 between blood & air in lungs Movement of substances across kidney tubules Movement of ions during the action potential

Osmosis
Net diffusion of water down its own concentration gradient Important in the movement of fluid across secretory epithelia e.g. lung epithelium & sweat gland Cell volume regulation

Carrier-mediated transport
Accomplished by membrane carrier protein Can be active transport or passive transport (facilitative diffusion) Characteristics that determine the kind and amount of material that can be transferred across the membrane Specificity Saturation Competition

Comparison of simple diffusion & facilitative diffusion

Rate of transport of molecule into cell

Simple diffusion down concentration gradient

Transport maximum or T m

Facilitated diffusion (carrier-mediated transport down concentration gradient) Substances move from a higher concentration to a lower concentration Requires protein carrier molecule Means by which glucose is transported into cells

Low ------------------------------------------------------ > High Concentration of transported molecules in ECF

Active transport
Moves a substance against its concentration gradient
Requires a protein carrier molecule Primary active transport Requires direct use of ATP, e.g. Ca2+ ATPase pump & NaK ATPase pump Secondary active transport Driven by an ion concentration gradient established by a primary active transport system, e.g. Na+-Ca2+ exchanger or Na+-glucose transporter in the GIT
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter6/animations.html#

Vesicular Transport - Active

Material is moved into or out of the cell wrapped in membrane Two types of vesicular transport
Endocytosis
Process by which substances move into cell Pinocytosis (cell drinking) nonselective uptake of ECF Receptor-mediated selective uptake of a large molecule, e.g. insulin and iron Phagocytosis selective uptake of multimolecular particle, e.g. neutrophils (leukocytes) phagocytose bacterial particles

Exocytosis
Provides mechanism for secreting large polar molecules, insulin & catecholamines
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter6/animations.html#

Measuring the Resting Membrane Potential (RMP)

Resting Membrane Potential (RMP)

A separation of charge exists across the membrane of all cells due to
an unequal distribution of key ions the selective permeability of the membrane the Na+K+ ATPase pump
pumps 2K+ into the cell for every 3Na+ out of the cell

A typical value of RMP is -70mV with reference to inside the cell

Terms to describe changes in membrane potential

Polarized means charged

e.g. RMP = -70mV

Depolarized means reduction in charge

e.g. -70mv goes to -30mV

Hyperpolarized means an increase in charge

e.g. -70mv goes to -90mV

Concentrations & permeability of ions responsible for the RMP in a typical mammalian cell
Concentration (mM) Extracellular Intracellular Relative Permeability

Ion

Na+

155

15

K+

160

50-75

A-

65

Cl-

70

50

Distribution of K+ ions
ECF ICF

+ K -

+
+
K+

Concentration gradient

Electrical gradient

+
+

+
+

Distribution of Na+ ions

ECF ICF

Concentration gradient + -

Na+

Na+
Cl

Electrical gradient

+
+ + +

Equilibrium Potential for an ion

Equilibrium is reached when there is no net flux of an ion
The voltage measured across the membrane at this point is called the equilibrium potential for that ion It can be calculated using the Nernst equation; E = 61 log Co CI where:

E= equilibrium potential for ion in mV 61 is a constant incorporating the universal gas constant (R), absolute temperature (T), the ions valence (z), an electrical constant Faraday (F) and the conversion of the natural logarithm (ln) to the logarithm to the base 10 (log); 61 = RT/zF Co is the extracellular concentration of ion (mM) Ci is the intracellular concentration of ion (mM)

Concentrations & permeability of ions responsible for the RMP in a typical mammalian cell
Concentration (mM) Extracellular Intracellular Relative Permeability

Ion

Na+

155

15

K+

160

50-75

A-

65

Cl-

70

50

Calculations
Calculate the EK, ENa and ECl 1. EK = 2. ENa = 3. ECl = What direction is the driving force for K+, Na+ and Cl- if the RMP is -70mV? 1. Driving force for K+ 2. Driving force for Na+ 3. Driving force for Cl-

Effect of concurrent K+ & Na+ movement on RMP

ECF EK ~ -90mV K+

+ K
2 K+
3 Na+

RMP = -70mV

Na+

Na+
ENa ~ 60mV

Action Potential in a single axon

+30

Approaches ENa
0

-50 -70 -90 1 2

threshold

Why is the RMP closer to EK than ENa?

Approaches EK

Summary
A typical value for the RMP is -70mV with reference to the ICF

Both K+ and Na+ ions play an important role in the establishment of the RMP
The equilibrium potential for a particular ion is the voltage at which there is no net movement of that ion The RMP is closer to EK, rather then ENa, because the resting membrane is more permeable to K+ At RMP neither K+ or Na+ ions are at equilibrium, hence passive diffusion of these ions is prevented by the action of NaK ATPase