Unit 2
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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 All
cells 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 • Passive transport
Simple diffusion F 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 Binding of the substrate at high concentration side causes conformational change. Compound released on low concentration side, causing return to original conformation.
•Rate of transport limited to number of available carrier proteins
Saturation of a Carrier Protein
Facilitated Diffusion of Ions Facilitated
diffusion 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 Internal
ligands 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.
Classification of Ion Channel
•Mechanically-gated ion channels ─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 transport protein that simutaneously transports two different molecules, in opposite directions, across the membrane
Antiport Na/H
§1.2 Movement of large
molecules across cell membrane Endocytosis
Exocytosis F
F
Phagocytosis Pinocytosis Receptor-mediated phagocytosis
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 transport passive
Carrier- Uses mediated Metabolic energy
Dependent on Na gradient
Simple diffusion
No
No
No
Yes
No
No No
Passive, downhill
Facilitated Passive, diffusion downhill Primary active transport
Active, uphill Yes
Yes, direct
Symport
Secondary active
Yes, indirect Yes, Solute move in same
Antiport
Yes
direction as Na across membrane
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
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 All
cells 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 • Passive transport
Simple diffusion F 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 Binding of the substrate at high concentration side causes conformational change. Compound released on low concentration side, causing return to original conformation.
•Rate of transport limited to number of available carrier proteins
Saturation of a Carrier Protein
Facilitated Diffusion of Ions Facilitated
diffusion 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 Internal
ligands 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.
Classification of Ion Channel
•Mechanically-gated ion channels ─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 transport protein that simutaneously transports two different molecules, in opposite directions, across the membrane
Antiport Na/H
§1.2 Movement of large
molecules across cell membrane Endocytosis
Exocytosis F
F
Phagocytosis Pinocytosis Receptor-mediated phagocytosis
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 transport passive
Carrier- Uses mediated Metabolic energy
Dependent on Na gradient
Simple diffusion
No
No
No
Yes
No
No No
Passive, downhill
Facilitated Passive, diffusion downhill Primary active transport
Active, uphill Yes
Yes, direct
Symport
Secondary active
Yes, indirect Yes, Solute move in same
Antiport
Yes
direction as Na across membrane
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
