Chapter 3B

Active Membrane Transport

• Two main types:

  • Active transport

  • Vesicular transport

• Both need ATP to move solutes through the plasma membrane because:

  • The solute is too big for channels.

  • The solute isn't lipid-soluble.

  • The solute can't move down the concentration gradient.

Active Transport

• Uses carrier proteins (solute pumps).

  • These proteins attach precisely and reversibly to the substance being moved.

  • Some carriers move multiple substances:

    • Antiporters: Move one substance into the cell while moving a different one out.

    • Symporters: Move two different substances in the same direction.

• Moves solutes against their concentration gradient (from low to high).

  • Needs energy (ATP).

Types of Active Transport

• Two types exist:

  • Primary active transport

    • The required energy comes directly from ATP hydrolysis.

  • Secondary active transport

    • The required energy is obtained indirectly from ionic gradients created by primary active transport.

Primary Active Transport

• Energy from ATP hydrolysis changes the shape of the transport protein.

• This shape change causes solutes (ions) attached to the protein to be pumped across the membrane.

• Examples include calcium, hydrogen (proton), and Na^+-K^+ pumps.

Sodium-Potassium Pump

• The most studied pump.

• It's an enzyme called Na^+-K^+ ATPase that pumps Na^+ out of the cell and K^+ back in.

• Found in all plasma membranes, especially active in excitable cells (nerves and muscles).

• Leakage channels in membranes cause Na^+ to leak into the cell and K^+ to leak out, moving down their concentration gradients.

• The Na^+-K^+ pump is an antiporter, pumping Na^+ out and K^+ in against their concentration gradients.

• Maintains electrochemical gradients, involving both the concentration and electrical charge of ions.

  • Essential for muscle and nerve tissue functions.

Primary Active Transport Definition: Solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP.

Secondary Active Transport

• Depends on the ion gradient created by primary active transport.

• Energy stored in gradients indirectly drives the transport of other solutes.

  • Low intracellular Na^+ concentration (maintained by the Na^+-K^+ pump) strengthens sodium's drive to enter the cell.

  • Na^+ can drag other molecules with it as it enters through carrier proteins (usually symporters).

• Some sugars, amino acids, and ions are transported into cells via secondary active transport.

Secondary Active Transport Definition: Is driven by the concentration gradient created by primary active transport.

Vesicular Transport

• Involves transporting large particles, macromolecules, and fluids across the membrane using membranous sacs called vesicles.

• Requires cellular energy (usually ATP).

Vesicular Transport Processes

• Include:

  • Endocytosis: Transport into the cell.

    • Types: phagocytosis, pinocytosis, receptor-mediated endocytosis.

  • Exocytosis: Transport out of the cell.

  • Transcytosis: Transport into, across, and then out of the cell.

  • Vesicular trafficking: Transport from one area or organelle to another within the cell.

Endocytosis

• Involves the formation of protein-coated vesicles.

• Usually involves receptors, making it a selective process.

  • The substance being pulled in must bind to its unique receptor.

  • Some pathogens can hijack receptors for cell entry.

• Once inside, the vesicle may:

  • Fuse with a lysosome, or

  • Undergo transcytosis.

Phagocytosis

• A type of endocytosis known as "cell eating."

• Membrane projections called pseudopods form and flow around solid particles, engulfing them into a vesicle.

• The formed vesicle is called a phagosome.

• Macrophages and certain white blood cells use phagocytosis.

  • Phagocytic cells move via amoeboid motion, where cytoplasm flows into temporary extensions.

Pinocytosis

• A type of endocytosis known as "cell drinking" or fluid-phase endocytosis.

• The plasma membrane infolds, bringing extracellular fluid and dissolved solutes inside the cell.

  • Fuses with an endosome.

• Used by some cells to "sample" the environment.

• The main way nutrient absorption occurs in the small intestine.

• Membrane components are recycled back to the membrane.

Receptor-Mediated Endocytosis

• Involves endocytosis and transcytosis of specific molecules.

• Many cells have receptors in clathrin-coated pits, which are internalized with the bound molecule.

  • Examples: enzymes, low-density lipoproteins (LDL), iron, insulin, and unfortunately, viruses, diphtheria, and cholera toxins.

• Caveolae have smaller pits and a different protein coat than clathrin but still capture specific molecules (folic acid, tetanus toxin) and use transcytosis.

Exocytosis

• The process where material is ejected from the cell.

• Usually activated by cell-surface signals or changes in membrane voltage.

• The substance being ejected is enclosed in a secretory vesicle.

• A protein on the vesicle (v-SNARE) finds and binds to target t-SNARE proteins on the membrane.

  • This docking process triggers exocytosis.

• Some substances exocytosed: hormones, neurotransmitters, mucus, cellular wastes.

Membrane Potential

Resting Membrane Potential (RMP)

• Electrical potential energy is produced by the separation of oppositely charged particles across the plasma membrane in all cells

  • The difference in electrical charge between two points is referred to as voltage.

  • Cells with a charge are said to be polarized.

• Voltage occurs only at the membrane surface.

  • The rest of the cell and extracellular fluid are neutral.

  • Membrane voltages range from -50 to -100 mV in different cells (the negative sign indicates the inside of the cell is more negative relative to the outside).

Role of Potassium (K^+) in RMP

• K^+ diffuses out of the cell through K^+ leakage channels down its concentration gradient.

• Negatively charged proteins cannot leave.

  • As a result, the cytoplasmic side of the cell membrane becomes more negative.

• K^+ is then pulled back by the more negative interior due to its electrical gradient.

• When the drive for K^+ to leave the cell is balanced by its drive to stay, RMP is established.

  • Most cells have an RMP around -90 mV.

• The electrochemical gradient of K^+ sets RMP.

Other Ions

• In some cells, Na^+ also affects RMP.

  • Na^+ is attracted to the inside of the cell due to the negative charge.

    • If Na^+ enters the cell, it can bring RMP up to -70 mV.

  • The membrane is more permeable to K^+ than Na^+, so K^+ has a more primary influence on RMP.

• Cl^- does not significantly influence RMP because its concentration and electrical gradients are balanced.

Active Transport and Electrochemical Gradients

• RMP is maintained through the action of the Na^+-K^+ pump, which continuously ejects 3Na^+ out of the cell and brings 2K^+ back inside.

• A steady state is maintained because the rate of active pumping of Na^+ out of the cell equals the rate of Na^+ diffusion into the cell.

• Neurons and muscle cells "upset" this steady-state RMP by intentionally opening gated Na^+ and K^+ channels.

Cell-Environment Interactions

• Cells interact with their environment by responding directly to other cells or indirectly to extracellular chemicals.

• Interactions always involve the glycocalyx.

  • Cell adhesion molecules (CAMs).

  • Plasma membrane receptors.

Cell Adhesion Molecules (CAMs)

• Every cell has thousands of sticky glycoprotein CAMs projecting from the membrane.

• Functions:

  • Anchor cells to the extracellular matrix or to each other.

  • Assist in the movement of cells past one another.

  • Attract WBCs to injured or infected areas.

  • Stimulate the synthesis or degradation of adhesive membrane junctions (e.g., tight junctions).

  • Transmit intracellular signals to direct cell migration, proliferation, and specialization.

Plasma Membrane Receptors

• Membrane receptor proteins serve as binding sites for various chemical signals.

  • Contact signaling: Cells that touch recognize each other by each cell’s unique surface membrane receptors.

    • Used in normal development and immunity.

  • Chemical signaling: Interaction between receptors and ligands (chemical messengers) that causes changes in cellular activities.

    • In some cells, binding triggers enzyme activation; in others, it opens chemically gated ion channels.

    • Examples of ligands: neurotransmitters, hormones, and paracrines.

• The same ligand can cause different responses in different cells, depending on the chemical pathway the receptor is part of.

• When a ligand binds, the receptor protein changes shape and becomes activated.

  • Some activated receptors become enzymes; others open or close ion gates, changing excitability.

  • Activated G protein-linked receptors indirectly cause cellular changes by activating G proteins, which can affect ion channels, activate other enzymes, or cause the release of internal second messenger chemicals, such as cyclic AMP or calcium.