Pathology Lectures

Carriers and Channels

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Slide 1 · Carriers and Channels

Plasma-membrane transport and cellular homeostasis

Robbins, Cotran & Kumar • Pathologic Basis of Disease • 11th ed.

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish lipid diffusion, channels, and carriers.

Explain passive versus active transport.

Trace the Na⁺ gradient to nutrient absorption.

Relate transport failure to cell swelling and injury.

Recognize transport-dependent drug resistance.

Slide 3 · Transport is essential for cell function

Cells must import nutrients and required ions.

Waste products must leave the cell.

Transport helps maintain ionic and osmotic conditions.

Membranes also regulate transport into organelles.

Plasma-membrane transport

Channel

Passive pore

Carrier

Passive or active

Transport maintains cellular homeostasis

Slide 4 · The lipid bilayer is a selective barrier

Small nonpolar molecules pass readily.

Glucose and charged ions are effectively excluded from free passage.

Specialized proteins provide selective routes across membranes.

EXTRACELLULAR

CYTOSOL

O₂

CO₂

H₂O

Na⁺

Cl⁻

Glu

Simple diffusion

Barrier to ions / glucose

Slide 5 · Simple diffusion does not use transport proteins

O₂ and CO₂ readily dissolve in the lipid bilayer.

Hydrophobic compounds may diffuse through the membrane.

Transport follows a favorable gradient.

X

X

X

X

X

X

X

Higher solute

Lower solute

Slide 6 · Water has two routes across membranes

Water can cross lipid bilayers at a low rate.

Aquaporins provide water-permeable channels.

Transport remains passive, directed by solute distribution.

EXTRACELLULAR

CYTOSOL

Na⁺

Hydrophilic pore

Slide 7 · Channels and carriers move small solutes

Channels provide a hydrophilic route.

Carriers bind solutes and change conformation.

Both enable selective movement otherwise restricted by the bilayer.

EXTRACELLULAR

CYTOSOL

Channel

Carrier

Slide 8 · Transporters are selective

Specificity can distinguish closely related solutes.

A transporter may recognize glucose but not galactose.

Selective transport prevents indiscriminate solute passage.

Carrier

Binding site

Glucose

Galactose

Selectivity differs among transporters

Slide 9 · Selectivity is not the same as permeability

The lipid bilayer limits entry of many polar species.

A transporter provides a route for a defined substrate.

Transport depends on the presence and properties of that protein.

EXTRACELLULAR

CYTOSOL

O₂

CO₂

H₂O

Na⁺

Cl⁻

Glu

Simple diffusion

Barrier to ions / glucose

Slide 10 · Channels form hydrophilic pores

An open channel creates a water-compatible pathway.

Solutes cross without the carrier-binding cycle.

Movement is usually restricted by size and charge.

EXTRACELLULAR

CYTOSOL

Na⁺

Hydrophilic pore

Slide 11 · Opening is required for channel conductance

A pore can conduct when it is open.

A closed channel does not provide the same continuous path.

The source defines channels by their open-pore function.

EXTRACELLULAR

CYTOSOL

Na⁺

Gate closed

Slide 12 · Channels distinguish ions by properties

Pore dimensions limit which species can pass.

Charge helps determine permissibility.

A channel is not a nonspecific hole through the bilayer.

EXTRACELLULAR

CYTOSOL

Na⁺

Hydrophilic pore

Small

Large

Size + charge restrictions

Slide 13 · Open channels can move solute rapidly

Hydrophilic pores allow rapid passage.

Movement is facilitated along a favorable gradient.

Channel transport does not drive solute uphill.

EXTRACELLULAR

CYTOSOL

Na⁺

Hydrophilic pore

Rapid when open

Slide 14 · Concentration gradients drive passive movement

A difference in concentration supplies a driving force.

Net movement tends from higher to lower solute concentration.

No direct ATP expenditure is required for this process.

X

X

X

X

X

X

X

Higher solute

Lower solute

Slide 15 · Cell membranes also have electrical gradients

Virtually all plasma membranes have a potential difference.

The inside is typically negative relative to the outside.

Electrical and concentration gradients both influence ions.

Outside

Inside (−)

+

+

+

−

−

−

Slide 16 · Electrochemical driving force combines two effects

Concentration differences favor redistribution of solute.

Electrical potential influences charged solutes.

Passive ion movement reflects the combined influence.

Concentration

Difference

Electrical

Difference

Net passive

Direction

Direction reflects both influences

Slide 17 · Carriers bind specific solutes

A substrate binds to the transporter.

Binding precedes transmembrane transfer.

The binding site helps determine transporter specificity.

EXTRACELLULAR

CYTOSOL

S

Specific solute-binding site

Slide 18 · Carrier movement requires conformational change

The protein changes its conformation.

The substrate is transferred across the bilayer.

This is distinct from passage through an open channel.

EXTRACELLULAR

CYTOSOL

S

Bind → change shape → release

Slide 19 · Carrier transport is relatively slow

The carrier must complete a conformational cycle.

Channels permit rapid transfer through an open pore.

The mechanistic distinction is central to transport classification.

EXTRACELLULAR

CYTOSOL

S

Bind → change shape → release

Slide 20 · Carriers may mediate passive transport

A carrier can move solute along a favorable gradient.

Transport need not consume ATP directly.

Classification depends on direction and energy coupling.

EXTRACELLULAR

CYTOSOL

S

Specific solute-binding site

Slide 21 · Channel versus carrier

CHANNEL

Hydrophilic pore

Fast when open

Size/charge selectivity

Passive solute movement

CARRIER

Binds specific substrate

Changes conformation

Relatively slower

Passive or active transfer

Active transport against a gradient requires carriers.

Slide 22 · Mechanism check: Identify the route

Which transport mechanism can move a solute against its concentration gradient?

A. An open channel alone

B. A suitably energized carrier

C. Simple diffusion through lipid

D. An unassisted aqueous pore

Slide 23 · Carrier transport can be active

B. A suitably energized carrier

Channels mediate passage along favorable gradients.

Active movement against a gradient requires an energy source.

Energy may come from ATP hydrolysis or a coupled ion gradient.

Slide 24 · Passive transport follows driving forces

The concentration gradient can power movement.

Electrical potential also influences ion transport.

Passive transport does not itself drive uphill movement.

Concentration

Difference

Electrical

Difference

Net passive

Direction

Direction reflects both influences

Slide 25 · Active transport moves solute uphill

The transported solute may move against its concentration gradient.

A carrier—not a channel—performs this task.

The process is energized by ATP or a coupled gradient.

ATP hydrolysis

Carrier moves solute against gradient

Slide 26 · Direct ATP use supports active carriers

Certain transporters are ATPases.

ATP hydrolysis provides energy for unfavorable solute movement.

The transport protein couples an energy reaction to transfer.

ATP hydrolysis

Carrier moves solute against gradient

Slide 27 · Ion gradients can indirectly power uptake

A pre-existing Na⁺ gradient can drive nutrient absorption.

The nutrient may move against its own concentration gradient.

ATP is not used directly by that apical cotransport event.

ATP-dependent

Na⁺ pump

Na⁺ gradient

Established

Nutrient uptake

Driven by Na⁺

Indirect ATP dependence

Slide 28 · Two routes to active transport

ATP-DRIVEN

ATP hydrolysis at the transporter

Energy expenditure is direct

Example: Na⁺,K⁺-ATPase

ION-GRADIENT-COUPLED

Uses an established ion gradient

ATP dependence is indirect

Example: Na⁺-linked apical nutrient absorption

Both require a carrier; Neither is channel-mediated uphill pumping.

Slide 29 · Na⁺,K⁺-ATPase generates a Na⁺ gradient

The membrane ATPase exchanges inorganic ions.

ATP use helps keep intracellular Na⁺ low.

That gradient becomes usable energy for other carriers.

EXTRACELLULAR

CYTOSOL

Na⁺/K⁺

ATPase

Na⁺ out

K⁺ in

ATP-driven ion exchange

Slide 30 · The Na⁺ gradient is a cellular energy resource

Na⁺ tends to enter along its gradient.

Coupled carriers exploit that tendency.

Nutrient uptake may proceed despite an opposing nutrient gradient.

ATP-dependent

Na⁺ pump

Na⁺ gradient

Established

Nutrient uptake

Driven by Na⁺

Indirect ATP dependence

Slide 31 · Apical nutrient carriers use Na⁺ coupling

An apical transporter brings nutrient into the cell.

Na⁺ entry provides the favorable driving step.

Na⁺,K⁺-ATPase sustains the requisite gradient.

LUMEN

EPITHELIAL CELL

BASOLATERAL SIDE

Na⁺ + nutrient

Na⁺ extrusion

Apical nutrient carrier

Na⁺/K⁺-ATPase

Na⁺ gradient links both proteins

Slide 32 · Intestinal epithelia use secondary active uptake

Apical nutrient transport may be Na⁺-linked.

Intracellular nutrient concentration need not be lower.

The driving gradient is maintained by Na⁺,K⁺-ATPase.

LUMEN

EPITHELIAL CELL

BASOLATERAL SIDE

Na⁺ + nutrient

Na⁺ extrusion

Apical nutrient carrier

Na⁺/K⁺-ATPase

Na⁺ gradient links both proteins

Slide 33 · Renal tubules exploit the same principle

Apical nutrient uptake can depend on Na⁺ influx.

Nutrient movement may oppose its own gradient.

Failure of the Na⁺ gradient compromises this transport logic.

LUMEN

EPITHELIAL CELL

BASOLATERAL SIDE

Na⁺ + nutrient

Na⁺ extrusion

Apical nutrient carrier

Na⁺/K⁺-ATPase

Na⁺ gradient links both proteins

Slide 34 · Nutrient uptake can oppose its own gradient

Favorable Na⁺ entry is coupled to nutrient movement.

The two solutes need not share the same concentration direction.

This is why indirect energy coupling matters.

ATP-dependent

Na⁺ pump

Na⁺ gradient

Established

Nutrient uptake

Driven by Na⁺

Indirect ATP dependence

Slide 35 · Application: Coupled absorption

An epithelial cell accumulates a nutrient above its extracellular concentration. What permits continued apical uptake?

A. The lipid bilayer alone

B. A channel with no energy coupling

C. A carrier coupled to the Na⁺ gradient

D. Water osmosis

Slide 36 · Na⁺ gradient supports apical nutrient uptake

C. A carrier coupled to the Na⁺ gradient

The nutrient can move against its gradient.

Na⁺ moves down a favorable gradient.

The Na⁺ gradient ultimately depends on ATPase activity.

Slide 37 · Multidrug-resistance proteins can be ATPases

Some transporter ATPases expel polar compounds.

Chemotherapeutic drugs are among the possible substrates.

Active export lowers cellular exposure to transported drugs.

EXTRACELLULAR

CYTOSOL

MDR

Transporter

Drug

Export of polar compounds

Slide 38 · Drug efflux can undermine chemotherapy

An MDR protein pumps certain drugs out of cells.

Tumor cells expressing the relevant transport mechanism may resist therapy.

This is a transport-mediated form of treatment resistance.

EXTRACELLULAR

CYTOSOL

MDR

Transporter

Drug

Export of polar compounds

Slide 39 · Water follows osmotic differences

Water movement is passive.

Solute concentration directs net water movement.

Tonicity therefore changes cell volume.

Cell

Na⁺

Na⁺

Na⁺

Water follows osmotic differences

Slide 40 · Hypertonicity promotes cell shrinkage

Extracellular salt exceeds the relative intracellular level.

Water leaves the cell.

Net water loss reduces cellular volume.

Cell

Na⁺

Na⁺

Na⁺

Na⁺

Na⁺

Na⁺

Water exits → cell shrinks

Slide 41 · Hypotonicity promotes cell swelling

Extracellular solute is relatively dilute.

Water enters the cell.

Net water gain increases cellular volume.

Cell

Na⁺

Water enters → cell swells

Slide 42 · Effect of external tonicity

HYPERTONIC ENVIRONMENT

Relatively high extracellular solute

Net water movement outward

Cell shrinks

HYPOTONIC ENVIRONMENT

Relatively low extracellular solute

Net water movement inward

Cell swells

Tonicity describes the direction of net water movement.

Slide 43 · The cytoplasm contains an osmotic load

Intracellular charged proteins attract counterions.

Metabolites also contribute to intracellular osmolarity.

Without compensation, water would accumulate.

Cell

Na⁺

Na⁺

Na⁺

Water follows osmotic differences

Slide 44 · Na⁺ extrusion protects against overhydration

Cells continuously expel small inorganic ions.

Membrane ion-exchanging ATPase activity is important.

Ion transport protects cell volume.

EXTRACELLULAR

CYTOSOL

Na⁺/K⁺

ATPase

Na⁺ out

K⁺ in

ATP-driven ion exchange

Slide 45 · Energy depletion disables volume control

Toxins or ischemia can impair cellular energy generation.

Ion pumping can then fail.

Osmotic imbalance produces swelling.

ATP depletion

Ion extrusion impaired

Osmotic water entry

Cellular swelling / rupture

Slide 46 · Ischemia can cause osmotic swelling

Ischemia limits the cell’s ability to generate energy.

ATP-dependent ion extrusion becomes insufficient.

Water accumulates and the cell swells.

ATP depletion

Ion extrusion impaired

Osmotic water entry

Cellular swelling / rupture

Slide 47 · Toxic injury can disrupt ion homeostasis

Certain toxins impair energy-dependent cell functions.

Reduced ion pumping permits osmotic water entry.

Persistent swelling can progress to rupture.

ATP depletion

Ion extrusion impaired

Osmotic water entry

Cellular swelling / rupture

Slide 48 · From pump failure to membrane rupture

Inorganic-ion removal becomes inadequate.

Intracellular osmotic pressure favors water entry.

The resulting swelling may culminate in cell rupture.

ATP depletion

Ion extrusion impaired

Osmotic water entry

Cellular swelling / rupture

Slide 49 · Ca²⁺ transport regulates cellular processes

Specialized transport systems control ion concentration.

Cytosolic enzymes can be regulated by Ca²⁺.

Ion homeostasis affects cellular function beyond volume.

Organelle

Transport across an internal membrane

Slide 50 · Cytosolic enzymes have a pH optimum

Transport helps control intracellular H⁺.

Many cytosolic enzymes are most active around pH 7.4.

Compartment-specific ion regulation supports enzyme activity.

Cytosol: ~pH 7.4

Lysosome: PH ≤5

Slide 51 · Lysosomes require an acidic compartment

Lysosomal enzymes function best at approximately pH 5 or less.

Internal membranes help maintain distinct conditions.

Cellular compartments depend on selective ion transport.

Cytosol: ~pH 7.4

Lysosome: PH ≤5

Slide 52 · Transport also occurs across organelle membranes

Channels and pores are not confined to the plasma membrane.

Membrane-separated compartments require controlled exchange.

Distinct ion concentrations support specialized functions.

Organelle

Transport across an internal membrane

Slide 53 · Bulk uptake is a different transport mode

Channels and carriers handle small solutes and ions.

Endocytosis internalizes fluid or larger material in vesicles.

Phagocytosis and pinocytosis represent forms of uptake.

EXTRACELLULAR

CYTOSOL

Vesicle

Large material packaged in vesicles

Slide 54 · Clinical mechanism check: Swelling

A cell exposed to an energy-depleting insult develops progressive swelling. Which sequence best explains it?

A. Reduced ion extrusion → osmotic water entry

B. Increased Na⁺ pumping → cell dehydration

C. An open solute channel → active ion export

D. Decreased intracellular osmolarity → water entry

Slide 55 · Osmotic swelling follows ion-pump failure

A. Reduced ion extrusion → osmotic water entry

Energy deprivation compromises ion-pump activity.

Intracellular osmotic burden promotes hydration.

Severe swelling may ultimately cause rupture.

Slide 56 · Mechanism check: Channel or carrier?

Select the statement consistent with Robbins’ transport description.

A. All channels can pump solutes uphill

B. Carriers must consume ATP for every movement

C. Open channels permit rapid gradient-driven movement

D. All small molecules cross the bilayer freely

Slide 57 · Channels enable rapid passive transfer

C. Open channels permit rapid gradient-driven movement

A hydrophilic pore allows rapid passage when open.

Carrier proteins bind substrate and undergo shape changes.

Active uphill transport requires a carrier.

Slide 58 · An integrated model of membrane transport

Permeability determines whether proteins are needed.

Gradient direction distinguishes passive from active transport.

ATPases maintain the ionic conditions on which cells depend.

Ion homeostasis determines cell volume and enzyme function.

Plasma-membrane transport

Channel

Passive pore

Carrier

Passive or active

Transport maintains cellular homeostasis

Slide 59 · Five principles to retain

Channels create selective hydrophilic pores.

Carriers bind solutes and change shape.

Only carriers mediate active uphill transport.

Na⁺ gradients drive intestinal and renal nutrient uptake.

Loss of ATP-dependent ion control causes osmotic swelling.

Slide 60 · Primary reference and source scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease

11th edition (2026) • Chapter 1: The Cell as a Unit of Health and Disease

Core section: “Carriers and Channels,” pp. 9–10.

Introductory background: “Membrane Transport” and “Passive Diffusion,” p. 9.

All diagrams are original, editable schematics. Clinical questions are hypothetical teaching applications of the cited principles.

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