Unit 2

Cellular Physiology
 Overview

 The cell membrane & its transport function

 Cell excitability, bioelectrical phenomena &
underlying mechanism
 Contraction of skeletal muscle
 Section 1
Structure of cell membrane &
transmembrane movement
 Importance
 Allcells acquire the molecules and ions they need
from their surrounding extracellular fluid (ECF).
There is an unceasing traffic of molecules and
ions.
– in and out of the cell through its plasma membrane
 Examples: glucose, Na+, Ca2+

– In eucaryotic cells, there is also transport in and out of

membrane-bounded intracellular compartments such
as the nucleus, endoplasmic reticulum , and
mitochondria.
 Examples: proteins, mRNA, Ca 2+ , ATP
 Two problems to be
considered:
 1. Relative concentrations
– Molecules and ions move spontaneously down
their concentration gradient (i.e., from a region
of higher to a region of lower concentration) by
diffusion.
– Molecules and ions can be moved against their
concentration gradient, but this process, called
active transport, requires the expenditure of
energy (usually from ATP).
 Two problems to be
considered:
 2.
Lipid bilayers are impermeable to
most essential molecules and ions.
– The lipid bilayer is permeable to water
molecules and a few other small, uncharged,
molecules like O2 and CO2. These diffuse freely
in and out of the cell. The diffusion of water
through the plasma membrane is of such
importance to the cell that it is given a special
name: osmosis.
 Lipid bilayers are not permeable to:
 ions such as
– K+, Na+, Ca2+ (called cations because when
subjected to an electric field they migrate
toward the cathode [the negatively-charged
electrode])
– Cl-, HCO3- (called anions because they migrate
toward the anode [the positively-charged
electrode])
 small
hydrophilic molecules like glucose
 macromolecules like proteins and RNA
 Solving These Problems
 Mechanisms by which cells solve the problem of
transporting ions and small molecules across their
membranes:
 Facilitated diffusion
Transmembrane proteins create a water-filled pore
through which ions and some small hydrophilic
molecules can pass by diffusion. The channels can be
opened (or closed) according to the needs of the cell.
 Active transport
Transmembrane proteins, called transporters, use the
energy of ATP to force ions or small molecules
through the membrane against their concentration
gradient.
 §1.1 Types of movement of
small molecule across cell
membrane
Simple diffusion F
• Passive transport
Facilitated diffusion F

Primary active transport

F
• Active transport

Secondary active
transport F
 Simple Diffusion
 Where substance moves across the membrane
in simple solution in water or lipid, Fick’s law
is obeyed and at any temperature the rate of
diffusion is proportional to the concentration
gradient across the membrane.
 The process is only weakly affected by
temperature and the rate is simply related to
the concentration gradient.
 It does nor saturate.
Simple diffusion –Depends on existing
concentration or
electrical gradient
–Depends on chemical
properties of transported
compounds
– Lipid soluble compounds,
O2 & CO2 are transported
by simple diffusion
Facilitated Diffusion of Molecules
 Substance that cannot cross the membrane by simple
diffusion (some small, hydrophilic organic
molecules, like sugars) may have their movement
facilitated by attachment to a carrier molecule
 Once again, the process requires transmembrane
proteins. Those molecules are passed through the
membrane by a conformational change in the shape
of the transmembrane protein when it binds the
molecule to be transported.
 Example: the plasma membrane of human red blood
cells contain transmembrane proteins that permit the
diffusion of glucose from the blood into the cell
 Carrier-mediated Facilitated Diffusion
•Involve carrier proteins
•Characteristics
–Specificity
•To a single type of
molecule

–Competition
–Saturation
•Rate of transport limited to
Binding of the substrate at high concentration side causes conformational number of available carrier
change. Compound released on low concentration side, causing return to proteins
original conformation.
Saturation of a Carrier Protein
Facilitated Diffusion of Ions
 Facilitateddiffusion of ions takes place
through proteins, or assemblies of proteins,
embedded in the plasma membrane. These
transmembrane proteins form a water-filled
channel through which the ion can pass
down its concentration gradient.
 Channel-mediated
Facilitated Diffusion
The transmembrane channels
that permit facilitated diffusion
can be opened or closed. They
are said to be "gated".

Channel can be gated by

voltage, ligand, mechanics
or light.

 Essential mechanisms
underlying bio-electrical
phenomena
 Ligand-gated Ion Channels
 Many ion channels open or close in
response to binding a small signaling
molecule or "ligand". Some ion channels
are gated by extracellular ligands; some by
intracellular ligands. In both cases, the
ligand is not the substance that is
transported when the channel opens.
External Ligands
 External ligands
(shown here in green)
bind to a site on the
extracellular side of
the channel.
 Examples:
– The binding of the
acetylcholine at
certain synapse.
Internal Ligands

 Internalligands bind to a site on the channel

protein exposed to the cytosol.
 Examples:
– "Second messengers", like cAMP and cGMP,
regulate channels involved in the initiation of
impulses in neurons responding to odors
(smell) and light respectively.
 •Mechanically-gated ion
Classification channels
of Ion Channel ─Open while mechanical
deformation of the cells
Stretch receptors
Sound wave
•Ligand gated ion channel
–Open in response to small
molecules that bind to proteins
or glycoproteins
•Voltage-gated ion channel
–Open when there is a change
in charge across the plasma
membrane
Comparison of Simple and
Facilitated Diffusion
Transport simply
moves down its
concentration gradient
from high [c] to low
[c] until equal

Passive Transport
displays saturation
kinetics, solute flows
only in the favored
direction
 Characteristics of Facilitated
Diffusion and Other Membrane
Protein Transporters
Specific for particular type of molecule or ion
Saturable at “high” concentration
Competition among similar molecules
Inhibited by drugs that bind to specific site
Regulated by second messengers
 Primary active transport
 Uses cellular Energy to
move compounds up or
against their concentration
gradient
 ATP is a source of
energy
 Established Gradient
Energy
 The role of Na+-K+ ATPase
• Na+-K+ ATPase accounts for >30% of total ATP
consumption
• Maintains 10-30 fold gradient for Na+ (out>in) and K+
(in>out)
• Inside negative membrane potential
• Large inwardly directed Na+ electrochemical gradient
• Many other transport processes couple to Na+ gradient
• For K+, electrical force balanced by concentration
gradient ⇒ near zero net gradient
 Secondary active transport
 Generated solute gradient (eg Na gradient) can be used
to drive uphill transport of second molecule
 Ions or molecules move in same (symport) or different
direction (antiport)
Example of Secondary
Active Transport
Symport: Na/Glucose
• An antiport is an
integral membrane Antiport Na/H
transport protein that
simutaneously
transports two
different molecules,
in opposite
directions, across the
membrane
 §1.2 Movement of large
molecules across cell
membrane
Phagocytosis
Endocytosis 

Pinocytosis
 F

  Receptor-mediated
phagocytosis
 Exocytosis
F
 Endocytosis
• Internalization of substances by formation
of a vesicle
Example of Endocytosis
 Exocytosis
•Accumulated vesicle secretions expelled from cell

•Examples
–Secretion of digestive
enzymes by pancreas
–Secretion of mucus by
salivary glands
–Secretion of mild by
mammary glands
Shown to top is an animation illustrating how secretion vesicles
approach the plasma membrane, fuse with the plasma membrane
and dump their soluble contents outside of the cell. This process is
called exocytosis and it is mechanism by which cells can secrete
molecules like proteins. The epithelial cells in the breast use
secretion vesicles to put the major protein of milk (casein) outside
of the cell which synthesized it.
 Summary of Membrane Transport
Type of Active or Carrier- Uses Dependent on Na
transport passive mediated Metabolic gradient
energy
Simple Passive, No No No
diffusion downhill

Facilitated Passive, Yes No No

diffusion downhill

Primary Active, uphill Yes Yes, direct No

active
transport
Symport Secondary Yes Yes, indirect Yes, Solute move in same
active direction as Na across membrane

Antiport Yes, Solute move in opposite

direction as Na across membrane
Summary
 Two adjacent sarcomeres are shown going through
cycles of contraction and relaxation. If the thin
filaments are attached to something such that a load
can be developed, tension will develop on the
sarcomeres as they shorten. Note that as the
sarcomere contracts, the Z lines move closer
together. The myosin thick filaments "walk" their
way along nearby actin thin filaments. Since the
structure of the thick filament allows the myosin to
"walk" in both directions and since the myosin
fibers do not stretch, the thin filaments of opposite
polarity are pulled together