UNC BIOL253 Evaluation 2 Study Guide

Content on cell membranes, diffusion, osmosis, membrane potentials, and neurophysiology

Functions of plasma membranes

1. Regulate the passage of substances into and out of cells and between cell organelles and cytosol

2. Detect chemical messengers arriving at the cell surface

3. Link adjacent cells together by membrane junctions

4. Anchor cells to the extracellular matrix

Structure of plasma membrane

made of phospholipid bilayer with embedded proteins (amphipathic integral or transmembrane proteins) and peripheral proteins (along surfaces of the membrane)

• Glycerol

• Fatty acids

• Phosphate groups

• Phospholipids

• Proteins

• Cholesterol

Fluid-mosaic model

concept of proteins freely moving about in the lipid bilayer of plasma membrane

Amphipathic

 a molecule that has both a hydrophilic (water-loving/polar/charged) region, and a hydrophobic (water-repelling/nonpolar) region within the same molecule

• spontaneously arrange themselves in water so that hydrophilic parts face water, and hydrophobic parts avoid water

• Ex. phospholipids

Transmembrane proteins (integrins)

Proteins that span the entire plasma membrane → part of the protein is inside the cell, while part is embedded inside the lipid bilayer, and another part extends outside the cell

Extracellular matrix (ECM)

A network of proteins and carbohydrates outside cells that provides structural support and biochemical signals to tissues

The role of integrins binding to the extracellular matrix

• Physical attachment: They form a mechanical link between the ECM and the cell interior (this is how cells stay anchored in tissues)

• Signal transduction (outside ←→ inside): integrins change shape and trigger intracellular signaling pathways for cells to receive information about mechanical stress, ECM composition, and tissues

• Cell junctions

How are cells packed together into tissue/organ types and how do they interact with neighboring cells/tissue?

Cells pack together using junctions, ECM, and membrane proteins

Interactions occur through:

• Direct contact

• Chemical signals

• Mechanical forces

• The structure of the tissue reflects its function

Desmosomes (anchoring junction)

Dense plaques (accumulated proteins), Cadherin proteins join plasma membranes of adjacent cells together, found in tissue subject to considerable stretching

Tight junction (occluding junction)

no space in between adjacent cells, occurs in a band around the entire cell (think like a belt), found in most epithelial cells, prevents paracellular movement of substances

Gap junction (communicating junction)

membrane proteins called connexins join cells together, allows for flow of small things like ions or small molecules, helps with electrical signal flow

Occluding junctions

seal cells together in an epithelium (prevents small molecules from leaking from one side to the other)

Anchoring junctions

mechanically attach cells (and their cytoskeleton) to their neighbors or the extracellular matrix

Communicating junctions

mediate passage of chemical or electrical signals from one interacting cell to its neighbor

How fast does plasma membrane turnover happen?

In minutes to hours

Factors that influence the rate of diffusion

1. Concentration gradient

2. Distance (path length) → thicker membranes or tissues slow diffusion down

3. Surface area → greater surface area = faster diffusion

4. Molecule size (molecular weight) → smaller molecules diffuse faster than larger ones

5. Temperature → high temperature = more kinetic energy = faster diffusion

6. Medium → diffusion is fastest in gases, slower in liquids, and slowest in solids

7. Membrane permeability

8. Electrical gradient (for ions)

What type of ions freely pass through the phospholipid bilayer?

• Freely: small, nonpolar molecules (O₂, CO₂, N₂, steroid hormones)

• Group 2: small, uncharged polar molecules (water, ethanol, glycerol)

• Group 3: larger, uncharged polar molecules (amino acids, glucose, nucleosides)

• Group 4: Ions (H⁺, Na⁺, K⁺, Ca²⁺, Cl^-, Mg²⁺, HCO₃^-)

Osmosis

net diffusion of water

Osmolarity

total solute concentration of a solution

Membrane permeability vs. osmotic pressure

Only solutes that cannot cross the membrane create lasting osmotic pressure

• depends on the number of non-penetrating solutes and the membrane permeability to those solutes

Membrane permeability vs. volume changes

Occurs when a membrane is permeable to water but not solutes

• solutes are trapped on one side

• Water moves towards higher solute concentration

• Causes cell to shrink (hypertonic) or swell (hypotonic)

Occurs when a membrane is permeable to some solutes

• Permeable solutes diffuse across the membrane

• Osmotic pressure decreases as solute concentrations equalize

• Penetrating solutes do not sustain osmotic pressure

Tonicity

he ability of a solution to change the volume of a cell by causing water to move across a semipermeable membrane

• depends only on non-penetrating (impermeable) solutes

• describes the effect on cell volume, not just solute concentration

• Types include isotonic, hypertonic, and hypotonic

Isotonic

no change in the cell volume (equal concentrations outside and inside the cell)

Hypertonic

cell shrinks (higher concentration in the environment than inside the cell)

Hypotonic

cell swells with water (higher concentration inside the cell than in the environment)

Examples of osmosis in healthcare

 IVs, kidney function, dialysis, digestion/nutrition, eye care, diuretics

Membrane potential

The electrical voltage difference across a cell’s plasma membrane, caused by an unequal distribution of charged ions between the inside and outside of the cell

• Measured in millivolts (mV)

  The inside of the cell is usually negative relative to the outside

• Typical resting membrane potential: neurons ~ -70mV, muscle cells ~ -90mV

Membrane permeability to specific ions

• At rest, membranes are most permeable to K⁺

  K⁺ leaks out through leak channels → inside becomes negative

  Opening or closing ion channels changes permeability and membrane potential

• Examples:

  • ↑ Na⁺ permeability → depolarization

  • ↑ K⁺ permeability → hyperpolarization

  • ↑ Cl⁻ permeability → stabilizes or hyperpolarizes membrane

Electrogenic pump (Na⁺/K⁺-ATPase)

Moves 3 Na⁺ out and 2 K⁺ in, creates and maintains ion gradients, and slightly contributes to negativity inside the cell

What are the two driving forces of the cellular electrochemical gradient?

1. Concentration gradient: difference in ion concentration across the membrane, ions move from high to low concentration

2. Electrical gradient: difference in electrical charge across the membrane, ions move toward opposite charges

Why might an H⁺-ATPase (proton pump) be useful in cells?

actively transports protons (H⁺) across a membrane using energy from ATP, creating proton gradients that the cell can use for multiple vital functions

• Generating an electrochemical gradient: Pumps H⁺ out of the cytoplasm

• Driving secondary transport: The proton gradient can be used to drive the transport of other molecules against their concentration gradient

  • H⁺ moving back down its gradient can co-transport nutrients (e.g., glucose, amino acids)

• Maintaining intracellular pH: Pumps H⁺ out of the cytoplasm to prevent acidification and keeps enzyme function and metabolism optimal

Why might an H⁺/K⁺-ATPase be found in acid secreting cells of the stomach?

it actively pumps protons (H⁺) into the stomach lumen in exchange for potassium (K⁺), creating the highly acidic environment needed for digestion

Mediated transport

the movement of molecules across a cell membrane with the help of specific proteins, because the molecules are too large, charged, or polar to diffuse freely through the lipid bilayer

Facilitated diffusion

• Direction: Down the concentration gradient (no energy required)

• Proteins involved: Carrier proteins or channels

• Examples and tissue specialization:

• Glucose transporters (GLUTs) in muscle and liver → allow glucose to enter cells when blood glucose is high

• Selective and faster than simple diffusion, but cannot move against a gradient

Primary active transport

• Direction: Against the concentration gradient (requires energy from ATP)

• Proteins involved: Pumps (ATPases)

• Examples and tissue specialization:

• Na⁺/K⁺-ATPase in all cells → maintains resting membrane potential and osmotic balance

• H⁺/K⁺-ATPase in stomach parietal cells → secretes acid for digestion

• Generates ion gradients used for signaling, volume control, and secondary transport

Secondary active transport

• Direction: Uses the gradient of one molecule to drive movement of another

• Proteins involved: Symporters or antiporters

• Examples and tissue specialization:

  • SGLT (sodium–glucose cotransporter) in kidney and intestine → uses Na⁺ gradient to absorb glucose

  • Na⁺/Ca²⁺ exchanger in cardiac muscle → removes calcium for muscle relaxation

• Relies on gradients established by primary active transport; efficient for nutrient absorption and ion homeostasis

Fanconi-Bickel Syndrome

No underlying enzymatic defect in carbohydrate metabolism had been identified, metabolism of both glucose and galactose is impaired, effects GLUT2 deficiency (SLC2A2 mutation), glycogen storage disease

Epithelial transport

• the movement of substances across an epithelial cell layer, from one side of the tissue to the other (for example, from the intestinal lumen into the blood)

• Transcellular pathway

• Paracellular pathway

Transcellular pathway

• Substance moves through the epithelial cells

• Uses channels, carriers, and pumps

• Highly selective and regulated

Paracellular pathway

• Substance moves between cells

• Passes through tight junctions

• Usually limited to small ions or water

Phagocytosis

a form of endocytosis in which specialized cells engulf large particles, such as bacteria, dead cells, or debris.

• Known as “cell eating”

• Performed mainly by immune cells (macrophages, neutrophils)

Pinocytosis

a form of endocytosis in which a cell nonspecifically engulfs extracellular fluid and dissolved solutes into small vesicles.

• Often called “cell drinking”

• Occurs continuously in most cells

Receptor-mediated endocytosis

a highly specific form of endocytosis in which ligands bind to cell-surface receptors, triggering vesicle formation.

• Uses clathrin-coated pits

• Allows efficient uptake of specific molecules (e.g., LDL cholesterol, hormone

Exocytosis

the process by which a cell releases substances to the outside by fusion of an intracellular vesicle with the plasma membrane.

• Used to secrete hormones, neurotransmitters, enzymes, and membrane proteins

• Can be constitutive (continuous) or regulated (stored then released)

Endocytosis

the process by which a cell brings substances into the cell by forming a vesicle from the plasma membrane.

• Requires energy

• Includes:

  • Pinocytosis

  • Phagocytosis

  • Receptor-mediated endocytosis

Trogocytosis

a process in which a cell extracts and internalizes small pieces of another cell’s plasma membrane during direct cell–cell contact.

• Common in immune cells (T cells, NK cells)

• Allows rapid cell-to-cell communication and signaling modulation

Apical membrane

faces fluid cavities, body surfaces

Basolateral membrane

lateral surfaces face other epithelial cells; basal cells face connective tissues

Volts (V)

difference in charge across a membrane

Resting membrane potential

the stable electrical voltage across the plasma membrane of a non-signaling cell, with the inside of the cell being negative relative to the outside.

• Typical values:

  • Neurons: ~ −70 mV

  • Muscle cells: ~ −90 mV

How resting membrane potential is maintained

1. Unequal ion distribution

• Na⁺: high outside, low inside

• K⁺: high inside, low outside

• Cl⁻: high outside

• Negatively charged proteins trapped inside the cell. These gradients create a tendency for ions to move.

2. Selective membrane permeability

• At rest, the membrane is most permeable to K⁺

• K⁺ leaks out through K⁺ leak channels

• Loss of positive charge leaves the inside negative

3. Electrical forces balance diffusion

• As K⁺ leaves, the interior becomes negative

• Electrical attraction pulls K⁺ back in

• Equilibrium between chemical and electrical forces stabilizes the voltage

4. Na⁺/K⁺-ATPase (ion pump)

• Pumps 3 Na⁺ out and 2 K⁺ in using ATP

• Maintains ion gradients

• Slightly increases the negative charge inside the cell

Membrane potential (Vₘ)

the electrical voltage difference across the plasma membrane, resulting from unequal distribution of ions and selective membrane permeability.

• Expressed in millivolts (mV)

• Inside of the cell is typically negative relative to the outside

Equilibrium potential

the membrane voltage at which there is no net movement of a specific ion across the membrane, because the electrical force exactly balances the chemical (concentration) gradient for that ion.

• Each ion has its own equilibrium potential (e.g., Eₖ, Eₙₐ)

• Calculated using the Nernst equation

Electrogenic pump

a membrane transport protein that moves unequal numbers of charges across the membrane, directly contributing to the membrane potential.

• Requires ATP

• Example: Na⁺/K⁺-ATPase (3 Na⁺ out, 2 K⁺ in)

How does the Na/K pump contribute to the membrane potential?

• It established the concentration gradient and creates a small negative potential

• Greater net movement of K+ out makes membrane more negative inside the cell

• Steady negative resting membrane potential, ion flux through channels balances each other

Overshoot

peak of positive potential (depolarization above 0 mV)

Graded potentials

• Occurs in a small region of the plasma membrane (localized)

• Magnitude can vary

• Decremental signals → become weaker as they get further from the origin

• No threshold and no refractory period

Action Potentials

• Large alterations in membrane potential

• Rapid and repeating

• Long-distance cell communication

• Voltage-gated ion channels

Characteristics of Na⁺ Channels

• Channel has 3 states:

  • closed (resting)

  • open

  • inactivated (open but inactivation gate is blocking the channel)

• Opens and inactivates very rapidly

Characteristics of K⁺ Channels

• Channel has 2 states:

  • Open

  • Closed

• Opens and closes slowly

Steps of an Action Potential

1. Steady resting membrane potential is near E_k, P_k > P_Na, due to leak K⁺ channels

2. Local membrane is brought to threshold voltage by a depolarizing stimulus

3. Current through opening voltage-gated Na⁺ channels rapidly depolarizes the membrane, causing more Na⁺ channels to open

4. Inactivation of Na⁺ channels and delayed opening of voltage-gated K⁺ channels halt membrane depolarization

5. Outward current through open voltage-gated K⁺ channels repolarizes the membrane back to a negative potential

6. Persistent current through slowly closing voltage-gated K⁺ channels hyperpolarizes membrane toward E_k; Na⁺ channels return from inactivated state to closed state (without opening)

7. Closure of voltage-gated K⁺ channels returns the membrane potential to its resting value

Function of Sodium Ion Channels

1. Depolarizing stimulus

2. Opening of voltage-gated Na⁺ channels

3. Increased permeability of P_Na

4. Increased flow of Na⁺ into the cell

5. Depolarization of the membrane potential leads to positive feedback loop

6. Eventual inactivation of Na⁺ channels

Function of Potassium Ion Channels

1. Depolarization of the membrane by Na⁺ influx

2. Opening of voltage-gated K⁺ channels

3. Increased P_K

4. Increased flow of K⁺ out of the cell

5. Repolarization of the membrane potential leads to negative feedback loop

Refractory Period

The short time after a cell (usually a neuron or muscle cell) fires an action potential during which it cannot fire again normally. It can be:

• Absolute

• Relative

Absolute refractory period

• No second action potential is possible, no matter how strong the stimulus.

• Happens because voltage-gated Na⁺ channels are inactivated.

• This guarantees that action potentials move in one direction only down the membrane

Relative refractory period

• A second action potential is possible, but only with a stronger-than-normal stimulus

• Occurs while K⁺ channels are still open and the membrane is hyperpolarized

• Some Na⁺ channels have reset, but some are still inactivated

Action potential propagation

• the movement of the action potential along the membrane of an axon or muscle cell

• The signal does not weaken as it travels (it’s all-or-none), because the action potential is regenerated at each segment of membrane

Saltatory conduction

• Myelin insulates the axon

• Action potentials occur only at Nodes of Ranvier

• Signal “jumps” node to node

• Much faster and more energy efficient

Nodes of Ranvier

small, unmyelinated gaps between adjacent myelin sheath segments along a myelinated axon

• Rich in voltage-gated Na⁺ (and K⁺) channels

• Site where action potentials are regenerated

• Enable saltatory conduction (the signal “jumps” from node to node)

Why might there be two different kinds of chemical synapses?

1. excitatory

2. inhibitory

the nervous system needs both acceleration and braking to function properly

Convergence of input

one cell is influenced by many others

Divergence of input

one cell influences many others

Steps of Activating a Presynaptic Cell

1. Action potential reaches axon terminal

2. Voltage-gated Ca²⁺ channels open

3. Calcium enters the axon terminal

4. Neurotransmitters are released and diffuse into the synaptic cleft

5. Neurotransmitters bind to their postsynaptic receptors

6. Neurotransmitters are removed from the synaptic cleft

Vesicle docking

the step in synaptic transmission where neurotransmitter-filled synaptic vesicles attach to the presynaptic membrane, positioning them for release

• Occurs at the active zone of the presynaptic terminal

• Mediated by SNARE proteins

• Puts vesicles in a ready-to-release state

After docking, an incoming action potential opens voltage-gated Ca²⁺ channels → Ca²⁺ enters → triggers vesicle fusion and exocytosis of neurotransmitter.

Synaptotagmin Function

the calcium sensor that triggers neurotransmitter release at chemical synapses

1. An action potential reaches the presynaptic terminal

2. Voltage-gated Ca²⁺ channels open → Ca²⁺ enters

3. Ca²⁺ binds to synaptotagmin on the synaptic vesicle

4. Synaptotagmin changes shape and interacts with SNARE proteins

5. This causes vesicle fusion with the presynaptic membrane and exocytosis of neurotransmitter

SNARE Proteins Function

Mediate synaptic vesicle docking and fusion by forming a complex that pulls the vesicle and presynaptic membranes together, enabling neurotransmitter release

• These proteins zip together, pulling the vesicle tightly against the membrane

• Provide the mechanical force needed for membrane fusion

• Ensure vesicles fuse at the correct location (active zone)

• Allow rapid, Ca²⁺-triggered exocytosis once synaptotagmin is activated

Partial fusion

• The vesicle briefly contacts the presynaptic membrane

• A small fusion pore opens

• Some neurotransmitter is released

• Vesicle then detaches and is recycled

• Fast and energy-efficient, allows rapid, repeated signaling

Complete fusion

• The vesicle fully merges with the presynaptic membrane

• All neurotransmitter is released

• Vesicle membrane becomes part of the presynaptic membrane

• Requires endocytosis to retrieve membrane

• ensures maximal transmitter release when needed

Ionotropic receptors

Ligand-gated ion channels that open directly upon neurotransmitter binding, allowing rapid ion flow and fast synaptic signaling

• Neurotransmitter binding causes an immediate conformational change

• Ions (Na⁺, K⁺, Ca²⁺, or Cl⁻) flow across the membrane

• Produce fast, short-lasting postsynaptic responses

• Generate EPSPs (depolarization) or IPSPs (hyperpolarization)

  • Examples: Nicotinic ACh receptors (neuromuscular junction), GABA

Metabotropic receptors

G-protein–coupled receptors that indirectly modulate ion channels or intracellular signaling pathways, producing slower but longer-lasting effects on the postsynaptic cell

• Neurotransmitter binding → receptor activates a G-protein

• G-protein can:

  • Open/close ion channels indirectly

  • Activate second messenger pathways (cAMP, IP₃, DAG)

• Effects are slower but longer-lasting than ionotropic responses

• Often produce modulatory effects rather than direct depolarization or hyperpolarization

• Examples: Muscarinic ACh receptors

Neurotransmitter Removal from Synapse

1. Enzymatic degradation → Ex. ACh broken down by acetylcholinesterase

1. Reuptake into presynaptic neuron → transporter proteins pump neurotransmitters back into the presynaptic terminal, they can be repackaged into vesicles or degraded by enzymes inside the neuron

2. Diffusion away from the synapse → then they can be taken up by nearby glial cells or diluted in ECF

Excitatory Postsynaptic Potentials (EPSPs)

depolarizing postsynaptic potential caused by excitatory neurotransmitter binding, which increases the likelihood of an action potential

• Caused by opening of ligand-gated ion channels (usually Na⁺ or Ca²⁺)

• Results in positive charge entering the postsynaptic cell → membrane potential moves closer to threshold

• Can summate (spatially or temporally) to trigger an action potential at the axon hillock

  • Example: ACh at nicotinic receptors

Inhibitory Postsynaptic Potentials (IPSPs)

a hyperpolarizing postsynaptic potential caused by inhibitory neurotransmitters, reducing the likelihood of an action potential

• Typically caused by Cl⁻ influx or K⁺ efflux through ligand-gated channels

Temporal Summation

the additive effect of multiple postsynaptic potentials occurring in quick succession at a single synapse

• Multiple EPSPs (or IPSPs) occur in rapid succession at the same synapse, and their effects add together

• If the summed depolarization reaches threshold → action potential fires

Spatial Summation

the combined effect of postsynaptic potentials from multiple synapses occurring simultaneously on a neuron

• The combined effect can bring the neuron to threshold or inhibit firing

Autoreceptors

presynaptic receptors that monitor and regulate the neuron’s own neurotransmitter release

• Regulate neurotransmitter release, often providing negative feedback to prevent excessive release

Axo-axonic neurons

neurons that synapse onto the axon of another neuron to regulate its neurotransmitter release

• Can modulate neurotransmitter release by either enhancing or inhibiting it (presynaptic inhibition or facilitation)