Cell Membrane

• The following notes cover cell membrane transition, communication, and second messengers.

Cell Membrane Composition

• The cell membrane consists of a phospholipid bilayer, with polar heads facing outward into watery environments and nonpolar tails forming the interior.
• Glycoproteins and glycolipids are present on the cell surface and are important for cell recognition.
• Proteins, both peripheral and integral, are embedded in the membrane, facilitating various functions.
• Cholesterol is present within the membrane, contributing to its fluidity and stability.

Membrane Proteins Functions

• Transport: Proteins facilitate the movement of specific molecules or ions across the membrane.
• Intercellular Joining: Membrane proteins connect cells together.
• Enzymatic Activity: Some membrane proteins act as enzymes, catalyzing reactions at the membrane surface.
• Cell-Cell Recognition: Proteins identify cells.
• Signal Transduction: Receptor proteins bind to signaling molecules and initiate a cellular response.
• Attachment: Proteins attach to the cytoskeleton and extracellular matrix, maintaining cell shape and stability.

Protein Channels

• Protein channels allow water and water-soluble molecules to pass through the cell membrane.
• Water channels are also known as aquaporins.
• Non-lipid-soluble molecules, such as water, can pass through protein channels if small enough.
• Ion channels allow ions like Na, K, Cl, and Ca to rapidly pass through the plasma membrane.
• Protein channels feature gates that control the permeability of the channel.

Ion Channels

• Some ion channels are always open (doorless), while others are temporarily opened and closed (gated).
• Membrane permeability to ions can rapidly change due to the opening and closing of gated channels.
• Voltage-gated channels are sensitive to voltage changes.
• Ligand-gated channels are sensitive to chemical changes.

Membrane Connections

• Gap junctions: These are for cell communication.
• Tight junctions: Create a tight seal.
• Desmosomes: Provide strong adhesion between cells.

Transport Across the Cell Membrane

• Passive transport: Molecules move down their concentration gradient, without cellular energy, e.g., diffusion and osmosis.
• Active transport: Requires cellular energy to move molecules against their concentration gradient, e.g., active transport, endocytosis, exocytosis, and phagocytosis.

Diffusion

• Diffusion is the movement of ions or molecules from an area of high concentration to an area of low concentration.
• Molecules and ions are in constant motion in body fluids.

Osmosis

• Osmosis occurs with water passing through a selectively permeable membrane from a less dense to a denser environment.

Tonicity Concepts

• Isotonic: The extracellular and intracellular environments have equal osmotic activity
• Hypertonic: Solutions with a higher solute concentration cause cells to shrink
• Hypotonic: Solutions with a lower solute concentration cause cells to swell

Active Transport Types

• Uniport: Transports a single molecule
• Symport: Transports two different molecules in the same direction
• Antiport: Transports two different molecules in opposite directions
• Primary active transport: Uses ATP directly.
• Secondary active transport: Uses ATP indirectly.

Endocytosis and Exocytosis

• Endocytosis: Transports substances from outside the cell to inside
• Exocytosis: Transports substances from inside the cell to outside
• These processes transport large molecules (proteins, polysaccharides, and polynucleotides).

Sodium-Potassium Pump

• Hydrolyzing an ATP molecule enables 3 Na ions to be moved out and 2 K ions to be moved into the cell.
• Sodium-potassium pump action is necessary for maintaining the cell volume.
• Without the pump, cells would swell and burst, the osmotic effect from water would not be in balance.

Chemical Messengers

• Cells communicate through intercellular chemical messengers.
• The six types of chemical messengers include paracrines, autocrines, neurotransmitters, neurohormones, hormones, and cytokines.
• Chemical messengers act on target cells when released into the extracellular fluid (ECF) upon appropriate stimulation.
• Chemical messengers differ in source and how they reach target cells.

Paracrines

• Paracrines target cells in the immediate environment of their release site.
• Paracrines operate via diffusion.
• Paracrines inactivated by local enzymes.

Autocrines

• Autocrines bind to receptors on the very cell that secreted them, regulating their own secretion.

Cytokines

• Cytokines are secreted, then diffuse to neighboring target cells.
• Cytokines are secreted and transported by blood to distant target cells.
• Interleukins and interferons are examples.

Neurotransmitters

• Neurotransmitters secreted from neurons at synapses.
• Neurotransmitters released from the axon terminal of a presynaptic cell that binds to receptors on a postsynaptic cell.
• Neurotransmitters act locally on a neuron, muscle, or a gland.

Hormones

• Hormones are secreted by endocrine cells into the interstitial fluid and enter the bloodstream.
• Hormones target cells with matching receptors.
• Cells lacking receptors are unresponsive to the hormone's signals.

Signal-Target Interaction

• There are basic cell membrane receptors:
• G-Protein dependent receptors
• Tyrosine-kinase receptors
• Ion channel receptors

First Messengers

• First messengers bind with specialized protein receptors on the plasma membrane.
• Hormones and neurotransmitters act as first messenger.
• Messenger + receptor triggers events like secretion and metabolism.

G-Protein Dependent Receptors

• They work with the help of a receptor known as the G-protein.
• The G-Protein is loosely attached to the cytoplasmic side of the membrane.

Binding of Extracellular Chemical Messenger

• Opening closing of specific ion channels
• Transfering the signal to an intracellular chemical messenger (second)

Second Messengers

• The binding of an extracellular chemical messenger brings about a desired cellular response.
• This happens by opening/closing specific channels or transfering the signal to an intracellular messenger.

G-protein-coupled receptors

• A neurotransmitter binds to a receptor resulting in effector protein.
• Then G-protein is activated.
• G-protein modulates ion channels.

Tyrosine-Kinase Receptors

• Monomers become a dimer structure.
• Activating transfer protein.

Ion Channel Receptors

• A ligand, a signalling molecule, binds its specific site on the membrane.
• A change in the shape of the channel proteins occurs, which causes concentration of an ion to modify.
• Stimulates electrical impulses

Intracellular Receptors

• Hydrophobic molecules pass from the membrane and bind their receptors inside the cell.
• Steroid and thyroid hormones, and NO are examples.

Protein Phosphorylation

• Protein phosphorylation is the basic signal transmission mechanism.

Activation of 2nd Messenger Systems

• Extracellular chemical messengers cannot enter cells. Instead, messengers bind to membrane, activation intracellular proteins.

Cyclic AMP Pathway

• Extracellular messenger + receptor activates adenylyl cyclase.
• G-protein acts as an intermediary.
• G proteins are bound to guanine nucleotides, guanosine triphosphate (GTP) or guanosine diphosphate (GDP).
• G proteins are on the inner surface of the plasma membrane.

Cyclic AMP Pathway Action

• The effector protein is the enzyme adenylyl cyclase.
• Adenylyl cyclase converts intracellular ATP to cAMP
• cAMP activates a cAMP-dependent protein kinase, which phosphorylates, and changes the shape of intracellular proteins
• Cyclic AMP activates a specific enzyme.

Calcium as a Second Messenger

• A first messenge binds to surface receptor G proteins and then activates phospholipase C.
• Next is phosphatidylinositol biphosphate or PIP₂.
• The last is diacylglycerol (DAG) and inositol triphosphate (IP₃).

Cyclic AMP and Calcium Pathways

• Pathways frequently overlap in bringing about a particular cellular activity.
• cAMP and Calcium can influence each other.
• Calcium activated calmodulin regulates adenylyl cyclase and cAMP.
• Cyclic AMP-dependent kinase phosphorylate and change the activity of Calcium channels or carriers.