Cell Physiology, Membrane Permeability, and Action Potentials

Flashcards covering cell membrane permeability, protein synthesis, organelle functions, electrophysiology, transport mechanisms, and homeostatic systems.

Substances that freely cross the selectively permeable plasma membrane vs. those that require transport proteins

• Freely cross: Small, nonpolar molecules ($O_2$, $CO_2$, steroid hormones)

• Require transport proteins/vesicles: Large molecules, ions, and charged substances ($Na^+$, $K^+$, $Cl^-$, glucose, proteins)

Effect of high temperature on plasma membrane fluidity and permeability

Increases phospholipid movement, making the membrane excessively fluid and permeable, which can cause ion leakage and disruption of gradients.

Effect of low temperature on plasma membrane fluidity and permeability

Decreases phospholipid movement, making the membrane rigid and less permeable, which impairs transport proteins, receptors, and enzymes.

Impact of fatty acid saturation on membrane fluidity

• Unsaturated fatty acids: Create double-bond kinks that prevent tight packing, increasing fluidity.

• Saturated fatty acids: Pack tightly, decreasing fluidity.

Impact of fatty acid tail length on membrane fluidity

• Shorter fatty acid tails: Increase membrane fluidity.

• Longer fatty acid tails: Decrease membrane fluidity.

Stabilizing role of cholesterol in biological membranes at high vs. low temperatures

• At high temperatures: Restrains phospholipid movement.

• At low temperatures: Prevents tight packing, buffering fluidity changes.

Four cellular parameters that can be altered to change membrane permeability

• Temperature

• Lipid composition

• Number/activity of transport proteins

• Opening/closing of ion channels

Strategies in drug delivery to enhance membrane crossing for non-permeable drugs

• Encapsulating in liposomes or nanoparticles

• Modifying lipid solubility or molecular charge

• Designing inactive prodrugs that activate inside target cells

Sequential steps of eukaryotic protein synthesis starting from DNA in the nucleus

1. DNA transcription to pre-mRNA by RNA polymerase

2. Pre-mRNA processing ($5'$ cap, splicing, poly-A tail)

3. mRNA export via nuclear pore

4. Ribosome binding and codon reading

5. tRNA amino acid delivery and peptide bond formation

6. Translation termination at stop codon

7. Folding and post-translational processing in ER/Golgi

Primary structure of a protein

The linear sequence of amino acids linked together by covalent peptide bonds.

Secondary structure of a protein

Local folding patterns into $\alpha$-helices and $\beta$-pleated sheets, stabilized primarily by hydrogen bonds along the polypeptide backbone.

Tertiary structure of a protein

The full three-dimensional folded shape of a single polypeptide chain, stabilized by side chain interactions (hydrogen bonds, ionic bonds, hydrophobic interactions, disulfide bridges).

Quaternary structure of a protein

The spatial arrangement and assembly of multiple polypeptide subunits into a functional protein complex (e.g., hemoglobin).

Enzyme contents and internal pH conditions of lysosomes

• Contents: Hydrolytic digestive enzymes (proteases, lipases, nucleases)
• Environment: Acidic interior maintained by active proton pumps

Role of lysosomes during phagocytosis of a bacterial cell

1. A phagocyte engulfs a bacterium into a phagosome.
2. The phagosome fuses with a lysosome.
3. Acidic hydrolytic enzymes digest and destroy the bacterium.

Primary physiological role of mitochondria

Production of cellular ATP through aerobic cellular respiration, specifically oxidative phosphorylation.

Structural reason why kidney tubular cells contain significantly more mitochondria than skin cells

• Kidney tubular cells: Perform continuous active transport requiring high amounts of ATP.
• Skin cells: Primarily serve protective barrier functions with low ATP needs.

Molecular mechanism and outcome of cyanide toxicity on mitochondria

• Mechanism: Cyanide blocks Complex IV of the electron transport chain.
• Outcome: Oxidative phosphorylation stops, ATP production drastically drops, leading to cellular pump failure and cell death.

Constitutive secretion vs. Regulated secretion

• Constitutive secretion: Occurs continuously without a triggering signal (e.g., extracellular matrix release).
• Regulated secretion: Stores materials in vesicles and releases them only after a specific signal, usually $Ca^{2+}$ influx (e.g., insulin or neurotransmitters).

Mechanisms for moving proteins into or out of the cell

• Exocytosis and endocytosis
• Protein translocation through translocons
• Nuclear pore transport
• ER-Golgi secretory pathway

Structure and function of tight junctions

Intercellular seals that join neighboring epithelial cells, preventing the paracellular movement of solutes and fluid (e.g., intestinal mucosa).

Structure and function of desmosomes

Strong mechanical cell-to-cell junctions that resist mechanical stretching and prevent tissues from pulling apart (e.g., skin).

Structure and function of gap junctions

Protein channels (connexons) connecting cytoplasm of adjacent cells, allowing direct passage of ions and small molecules for electrical/chemical communication (e.g., cardiac tissue).

Structure and function of hemidesmosomes

Specialized cellular structures that anchor the basal surface of epithelial cells to the underlying extracellular matrix or basement membrane.

Distinction between physiology and pathophysiology

• Physiology: Study of normal function in living organisms.
• Pathophysiology: Study of altered mechanisms caused by disease or injury.

Major organ systems regulating arterial blood pressure

• Cardiovascular system
• Nervous system: Autonomic rapid control
• Renal system: Long-term volume control
• Endocrine system: RAAS regulation

Pathophysiological consequence of losing homeostatic control

Internal variables shift outside normal physiological limits, leading to cellular stress, tissue damage, disease, organ dysfunction, or death.

Intracellular fluid (ICF) compartment volume and primary cation

• Volume: Contains approximately $\frac{2}{3}$ of total body water
• Primary Cation: High concentration of $K^+$ ions

Extracellular fluid (ECF) compartment volume, divisions, and primary cation

• Volume: Contains approximately $\frac{1}{3}$ of total body water
• Divisions: Plasma and interstitial fluid
• Primary Cation: High concentration of $Na^+$ ions

Physiological effect of abnormal plasma protein leakage into interstitial fluid

Increases interstitial fluid colloid osmotic (oncotic) pressure, drawing water out of blood vessels into tissues and causing tissue edema.

Relationship between Mean Arterial Pressure (MAP), Cardiac Output (CO), and Total Peripheral Resistance (TPR)

• $\text{MAP} \approx \text{CO} \times \text{TPR}$
• $\text{CO} = \text{HR} \times \text{SV}$

Behavior of arterial blood $O_2$ and $CO_2$ levels during moderate exercise

Arterial $O_2$ and $CO_2$ levels remain relatively constant because respiratory ventilation and cardiac output increase proportionally to match metabolic consumption/production.

Thermoregulatory responses initiated when external body temperature rises

• Skin blood vessels: Vasodilation (increases radiant heat loss)
• Sweat glands: Sweat secretion (evaporative cooling)

Thermoregulatory responses initiated when external body temperature drops

• Skin blood vessels: Vasoconstriction (conserves core heat)
• Skeletal muscles: Shivering thermogenesis (generates metabolic heat)

Ordered sequence of components in a homeostatic reflex loop

1. Stimulus
2. Receptor
3. Afferent pathway
4. Integrating center
5. Efferent pathway
6. Effector
7. Response

Five major classes of chemical signaling molecules in the human body

• Hormones
• Neurotransmitters
• Cytokines
• Growth factors
• Paracrine/autocrine mediators (e.g., histamine, nitric oxide)

Effect of a high dietary intake of $Na^+$ on the action potential depolarization phase

Increases the extracellular $Na^+$ concentration, strengthening the electrochemical driving force for $Na^+$ entry upon channel opening, boosting depolarizing drive.

Effect of a high dietary intake of $K^+$ on the resting membrane potential

Increases extracellular $K^+$, reducing the concentration gradient driving $K^+$ exit, causing the resting membrane potential to become partially depolarized.

Physiological rationale for administering epinephrine during cardiac arrest

Stimulates $\alpha$- and $\beta$-adrenergic receptors to increase:

• Heart rate
• Myocardial contractility
• Impulse conduction
• Systemic blood pressure

Three primary contributors to establishing a negative resting membrane potential

• $K^+$ leak channels ($K^+$ efflux)
• $Na^+/K^+$ ATPase pump ($3\text{ }Na^+$ out / $2\text{ }K^+$ in)
• Impermeable intracellular negatively charged proteins and organic anions

Single greatest direct contributor to resting membrane potential in neurons

Passive $K^+$ efflux through persistent $K^+$ leak channels.

Mechanism of action of local anesthetics on nerve signaling

Block voltage-gated $Na^+$ channels, preventing inward $Na^+$ current, stopping action potential generation and propagation along sensory nerve fibers.

Primary ion channel event responsible for bringing a hyperpolarized membrane back to rest

Closure of voltage-gated $K^+$ channels, stopping excess $K^+$ efflux.

Effect of a mutation inactivating voltage-gated $K^+$ channels on muscle tissue

Impairs membrane repolarization due to decreased $K^+$ efflux, maintaining sustained depolarization and leading to continuous, unrelaxed muscle contractions.

Stimulus requirements for firing an action potential during the relative refractory period

Requires a stronger-than-normal depolarizing stimulus because the membrane is hyperpolarized and some $Na^+$ channels remain inactivated.

Absolute Refractory Period vs. Relative Refractory Period

• Absolute Refractory Period: No action potential can be triggered regardless of stimulus strength due to $Na^+$ channel inactivation.
• Relative Refractory Period: A stronger-than-threshold stimulus can trigger an action potential.

Effect of loss-of-function mutations in voltage-gated $Na^+$ channels

Prevents rapid membrane depolarization, blocking action potential initiation and leading to nerve loss of sensation or muscle paralysis.

Cellular consequences of improper protein folding

• Loss of normal biological function
• Degradation by proteasomes
• Refolding by chaperones
• Pathological protein aggregation

Caloric energy density of lipids compared to carbohydrates and proteins

• Lipids: $\approx 9\,\text{kcal/g}$
• Carbohydrates & Proteins: $\approx 4\,\text{kcal/g}$

Structural reason why lipid oxidation yields more energy per gram than carbohydrates

Fatty acid chains contain a higher proportion of highly reduced $C-H$ bonds, yielding significantly more electrons for ATP production per gram.

Primary organelle responsible for protein modification, sorting, and packaging

The Golgi apparatus.

Transcription definition and primary enzyme involved

• Definition: The synthesis of an mRNA copy from a DNA gene template.
• Enzyme: RNA polymerase in the nucleus.

Translation definition and cellular location

• Definition: The decoding of mRNA codons into a specific amino acid sequence.
• Location: Ribosomes in the cytoplasm or on the rough ER.

Functions of the Nucleus and Nucleolus

• Nucleus: Stores genomic DNA and controls gene transcription.
• Nucleolus: Synthesizes ribosomal RNA ($rRNA$) and assembles ribosomal subunits.

Functions of the Rough ER and Smooth ER

• Rough ER: Synthesizes and folds membrane-bound, organelle-targeted, or secreted proteins.
• Smooth ER: Synthesizes lipids, metabolizes carbohydrates, detoxifies drugs, and stores $Ca^{2+}$.

Functions of Peroxisomes and Endosomes

• Peroxisomes: Oxidize fatty acids and detoxify toxic substances ($H_2O_2$ breakdown).
• Endosomes: Sort internal material endocytosed from the cell surface.

Microfilaments (actin filaments): Size and primary functions

• Size: Smallest cytoskeletal filaments ($\approx 7\,\text{nm}$)
• Functions: Maintain cell shape, form microvilli, drive cell movement, cytokinesis, and muscle contraction with myosin.

Intermediate filaments: Size and primary functions

• Size: Medium cytoskeletal fibers ($\approx 10\,\text{nm}$)
• Functions: Provide high mechanical tensile strength, anchor organelles, and resist stretching forces (e.g., keratin, desmin).

Microtubules: Size and primary functions

• Size: Largest cytoskeletal components ($\approx 25\,\text{nm}$)
• Functions: Form intracellular transport tracks, construct the mitotic spindle, and form cilia and flagella.

Ion channel types responsible for generating graded potentials

• Ligand-gated (chemically gated) channels
• Mechanically gated channels

Role of fixed intracellular anions on membrane potential

Impermeable intracellular proteins and organic phosphates carry fixed negative charges, attracting cations and helping establish internal negativity.

Effect of increasing stimulus strength on action potential magnitude vs. frequency

• Amplitude: Remains constant (all-or-none).
• Frequency & Recruitment: Stronger stimuli increase action potential frequency and recruit additional fibers.

Mechanism of action of epidural anesthesia

Blocks voltage-gated $Na^+$ channels in spinal nerve roots, inhibiting sensory pain signal transmission while sparing larger motor fibers at appropriate doses.

Status of voltage-gated ion channels during resting membrane potential ($-70\,\text{mV}$)

• Voltage-gated $Na^+$ & $K^+$ channels: Closed
• $K^+$ leak channels: Open

Status of voltage-gated ion channels during action potential depolarization phase

• Voltage-gated $Na^+$ channels: Open rapidly, allowing mass $Na^+$ influx.
• Voltage-gated $K^+$ channels: Begin opening slowly.

Status of voltage-gated ion channels at the action potential peak ($+30\,\text{mV}$)

• Voltage-gated $Na^+$ channels: Close their inactivation gates.
• Voltage-gated $K^+$ channels: Fully open.

Status of voltage-gated ion channels during action potential repolarization phase

• Voltage-gated $Na^+$ channels: Inactivated / resetting
• Voltage-gated $K^+$ channels: Open, causing rapid $K^+$ efflux.

Status of voltage-gated ion channels during hyperpolarization ($-80\,\text{mV}$)

• Voltage-gated $Na^+$ channels: Reset to closed state.
• Voltage-gated $K^+$ channels: Slowly closing, causing temporary excess $K^+$ efflux.

Mechanism of action and physiological consequences of Tetrodotoxin (TTX)

• Mechanism: Physically blocks the pore of voltage-gated $Na^+$ channels.
• Consequences: Stops $Na^+$ flux and action potentials, causing numbness, muscle paralysis, and respiratory arrest.

Endocrine vs. Paracrine signaling

• Endocrine: Chemical signal (hormone) travels via bloodstream to distant target tissues.
• Paracrine: Chemical signal diffuses locally through interstitial fluid to affect nearby cells.

Autocrine vs. Synaptic vs. Contact-dependent signaling

• Autocrine: Signal acts on the releasing cell.
• Synaptic: Neurotransmitters diffuse across a synaptic cleft.
• Contact-dependent: Surface membrane molecules interact directly on adjacent cells.

Effect of hypokalemia (low extracellular $K^+$) on cellular excitability

• Increases $K^+$ concentration gradient, driving $K^+$ out, hyperpolarizing the membrane, moving it further from threshold, and reducing excitability.

• Irregular heartbeat, can stop heart

Key distinctions between Graded Potentials and Action Potentials

• Graded Potentials: Variable amplitude, local/decaying, no threshold or refractory period, can summate.
• Action Potentials: All-or-none, fixed amplitude, self-propagating without decay, possesses refractory periods.

Cytoplasm vs. Cytosol

• Cytoplasm: Includes cytosol plus all membrane-bound organelles and inclusions.
• Cytosol: Refers strictly to the fluid portion of the cytoplasm.

Lateral movement vs. Transverse movement (flip-flop) of membrane phospholipids

• Lateral movement: Rapid movement within the same membrane leaflet.
• Transverse movement (flip-flop): Extremely rare spontaneous movement between inner and outer leaflets.

Plasma membrane adaptations promoting fluidity in cold-adapted organisms

• Increased proportion of unsaturated fatty acid chains
• Shorter fatty acid tail length

Cellular junction responsible for preventing paracellular absorption in the intestinal mucosa

Tight junctions (zonula occludens).

Molecular motors for long-distance transport along axonal microtubules

• Kinesin: Anterograde transport (toward plus end / cell periphery)
• Dynein: Retrograde transport (toward minus end / cell center)

Simple diffusion vs. Facilitated diffusion

• Simple diffusion: Nonpolar molecules pass directly through lipid bilayer down gradient without proteins.
• Facilitated diffusion: Polar/charged solutes pass down gradient using channel or carrier proteins.

Functional classifications of membrane transport proteins

• Ion channels: Gated pores
• Carrier proteins: Conformational changers
• Active transport pumps: ATP-driven

Active transport vs. Passive transport

• Active transport: Moves solutes against their electrochemical gradient using energy (ATP or ion gradient).
• Passive transport: Moves solutes down gradient without cellular energy.

Three main gating mechanisms of ion channels

• Voltage-gated (change in membrane potential)
• Ligand-gated (binding of chemical ligand)
• Mechanically gated (physical membrane deformation)

Definition of Osmosis

The net movement of water across a selectively permeable membrane toward a region of higher nonpenetrating solute concentration.

Three major types of endocytosis

• Phagocytosis: 'Cell eating' of large particles
• Pinocytosis: 'Cell drinking' of fluid
• Receptor-mediated endocytosis: Selective intake via coated pits

Directional difference between Exocytosis and Endocytosis

• Exocytosis: Exports intracellular vesicle contents out of the cell.
• Endocytosis: Imports extracellular materials into intracellular vesicles.

Structural arrangement of the Fluid Mosaic Model

A dynamic phospholipid bilayer with hydrophilic heads facing outward, hydrophobic tails facing inward, embedded with proteins, cholesterol, and surface carbohydrates.

Components and functions of the Extracellular Matrix (ECM)

• Components: Fibrous proteins (collagen, elastin), glycoproteins (fibronectin), and proteoglycans
• Functions: Provides structural support, cell attachment, and tissue organization

Definition of Cell Differentiation

The process by which unspecialized stem cells acquire specialized structural features and physiological functions through selective gene expression.

Negative feedback control mechanism definition and example

• Definition: A control loop where the physiological response opposes or reverses the original stimulus to maintain stability.
• Example: Insulin secretion lowering high blood glucose.

Positive feedback control mechanism definition and example

• Definition: A control loop where the physiological response amplifies or reinforces the initial stimulus until a definitive endpoint is reached.
• Example: Oxytocin during labor or blood clotting cascade.

Feedforward control mechanism definition and example

• Definition: A control mechanism that initiates adaptive physiological responses in anticipation of an impending change.
• Example: Cephalic phase salivation before eating.

Ordered sequence of components in a neuronal reflex arc

1. Sensory receptor
2. Sensory (afferent) neuron
3. Integration center (CNS interneuron)
4. Motor (efferent) neuron
5. Effector muscle/gland

Purpose and components of the Goldman-Hodgkin-Katz (GHK) equation

Calculates total membrane potential at rest by accounting for concentration gradients and relative membrane permeabilities of multiple ions ($Na^+$, $K^+$, $Cl^-$) simultaneously.

Nernst Equation vs. Goldman-Hodgkin-Katz (GHK) Equation

• Nernst Equation: Calculates equilibrium potential for a single ion.
• GHK Equation: Calculates actual membrane potential considering multiple ions and their permeabilities.

Effect of a hypertonic environment on cell volume

Water exits the cell by osmosis toward higher solute concentration outside, causing the cell to shrink and crenate.

Effect of a hypotonic environment on cell volume

Water enters the cell by osmosis toward higher solute concentration inside, causing cell swelling and potential lysis (hemolysis in RBCs).

Characteristics and effect of an isotonic solution on cells

Has an equal concentration of nonpenetrating solutes compared to intracellular fluid, causing no net water movement and preserving cell volume.

Clinical risk of administering pure distilled water (severely hypotonic IV fluid)

Causes massive osmotic water influx into red blood cells and brain cells, leading to hemolysis, cerebral edema, and cell death.

Tonicity vs. Osmolarity

• Osmolarity: Counts total solute particle concentration.
• Tonicity: Depends specifically on nonpenetrating solute concentration and determines cell volume changes.

Stoichiometry of the Sodium-Potassium Pump ($Na^+/K^+$ ATPase) per ATP molecule

Actively transports $3\text{ }Na^+$ ions OUT of the cell and $2\text{ }K^+$ ions INTO the cell per $1$ ATP hydrolyzed.