Midterm 1 Flashcards
What are the most important features of the body’s milieu interieur?
most important features of the body’s internal environment: stable, compensates + equilibrates organs of the body against changes in the external environment with different systems
ex) temperature regulation, pH balance, ion concentration
Explain what homeostasis is and why it is central to the study of physiological systems.
maintaining internal environment; exists in a system when its critical parameters are successfully regulated
ensures maintenance of optimal conditions for cellular function and adapt to external changes (react to stimuli) by integrating multiple systems; understanding disease
Example of physical law and empirical relationship.
Poiseuille’s Law: resistance to flow in a tube is inversely proportional to radius^4; constriction, smaller radius, increased resistance, reduction in blood flow
Starling’s Length-Tension Diagram for the heart: increase in end-diastolic volume (heart chamber more blood) causes increase in systolic pressure (force of contraction)
What are the basic elements of the feedback control pathway and what is its function?
coordinating center with set-point, command signal, effector, detector, feedback to achieve homeostasis
Example of negative feedback
Control of Mean Arterial Pressure
1. coordinating center: medulla receives signal for low BP
2. command signal: efferent pathways send signals down the nerves to heart + blood vessels to increase HR + vasoconstriction
3. effector: heart and vessels
4. detector: baroreceptors
5. feedback: afferent pathways
What are the functions of the cellular plasma membrane?
- separates cell’s contents from the environment
- enable formation of cells into tissues and organs
- enable solute transport
- enables cell excitability (electrical activity)
- enables signaling and communication
What are the chemical properties of phospholipids and how does this allow for self-assembly into membranes? What properties do membranes have as a result?
amphipathic: hydrophobic fatty acid tails, glycerol backbone, phosphate group (negative charge), hydrophilic head group
self-assembly into a fluid bilayer with selective permeability forms a barrier in aqueous environment
What molecules are impermeable, permeable, and semi-permeable to the membrane?
Impermeable: charged substances (ions, amino acids, proteins), larger polar molecules (glucose)
Semi-permeable: small, polar molecules (water)
Permeable: hydrophobic molecules (O2, CO2, steroid-type hormones like cholesterol/testosterone)
What is the relationship between electrochemical gradients and the direction of movement of ions across membranes?
ions move down their electrochemical gradient: difference in concentration and difference in charge (electrical potential (V) difference)
What are the roles of integral membrane proteins?
- facilitate molecular transport (pores, channels, carriers, pumps for H2O soluble)
- serve as adhesion molecules
- anchor the cyotskeleton to the membrane
- act as receptors
- act as enzymes
Explain the differences between the nature of molecular movement (how flux varies with concentration gradient) through pores, channels, and carriers.
Pores: non-gated channel (always open), passive diffusion, selective for ion or molecule; for uncharged, flux is proportional to concentration gradient
Channels: can be voltage or ligand gated, passive diffusion, selective for particular molecule (often ions), flux is always proportional to concentration gradient
Carriers: 2 doors that are never open at the same time, GLUT1 glucose transporter; saturation point (no active sites open) above which flux can’t rise (enzyme kinetics)
What are the roles of integral proteins in cell adhesion (specifically in tight and gap junctions)?
tight junction: prevents solvent passage between cells (form barriers)
gap junction: cell to cell communication (form channels to synchronize activity)
- includes integrins, cadherins, and claudins
What are the different categories of receptor proteins and how do they play a role in transduction of signals across membranes?
- Ligand-gated channels: bind specific molecule that causes conformational change (allows ions to pass)
- Receptors with catalytic activity: upon ligand binding, have enzymatic activity (often receptor tyrosine kinase, insulin)
- G-protein coupled receptors: upon ligand binding, activates an associated G-protein
What are the special properties of G-protein-coupled receptors and explain why their structure provides diversity and modularity of signaling?
Receptor consists of 7 membrane spanning segments; has diverse extra + intracellular sides (ligands + G-proteins) == highly modular and versatile signaling
- ligand binds to GPCR
- receptor interacts with G-protein (alpha, beta, gamma) to promote conformational change that exchanges GDP for GTP
- activates effector pathway
What is the difference between autocrine, paracrine, and endocrine signaling? How do these modes of signaling require signaling ligands with different properties?
autocrine: cell releases signal that act on receptors on the same cell (cancer promotes own growth); short-lived, bind quickly
paracrine: localized, limits activity of signal to desired area (NMJ); short-lived
endocrine: long-range; hormones that travel through the bloodstream; stable, high-affinity receptors
signaling molecules or ligands include:
1. amines (epinephrine)
2. peptides and proteins (insulin)
3. steroids (estrogen)
4. small molecules (AA, nucleotides, gasses)
What is the distribution of body fluids in body compartments? What are the concentration of ions in each?
intracellular fluid: 25 L; [Na+] = 15 mM, [K+] = 120 mM, [Cl-] = 20 mM
- separated by plasma membrane
extracellular fluid
- blood plasma (separated by capillary endothelium): 3 L; [Na+] = 142 mM, [K+] = 4.4 mM, [Cl-] = 102 mM
- interstitial fluid: 13 L; [Na+] =145 mM, [K+] =4.5 mM, [Cl-] =116 mM
- transcellular fluid (separated by epithelial cells): 1 L; variable ion concentration
Total = 42 L
Every compartment has equal osmolarity (290 mM)
How do concentration differences, electrochemical potential, and membrane permeability contribute to rate of transport across biological barriers?
Concentration Differences
- molecules move from high to low concentration
- chemical potential energy created from gradient = RTln([Xin]/[Xout])
Electrochemical Potential
- Combines concentration gradient and electrical gradient (high to low potential)
- Drives ion movement across membranes
Membrane Permeability
- Lipid Bilayer: Permeable to small, nonpolar molecules
- Transport Proteins: Required for larger, polar molecules
- Membrane fluidity impacts permeability
What parameters affect the rate of transport for uncharged solutes?
Fick’s Law: Jx (mol/t*area) = Px(Cout-Cin) = Px([Xo]-[Xin])
permeability coefficient (Px) = DB/dx
diffusion coefficient (D): rate
barrier thickness (dx): membrane
partition coefficient (B): solubility of molecule in lipid
What is the principle of bulk electroneutrality?
the number of positive charges in the overall solution must be the same as the number of negative charges
all fluid compartments must satisfy this
deviations of this occur at membranes at undetectable numbers of molecules
How does an ionic gradient generate an electrical potential energy across the membrane?
total driving force = voltage driving force + concentration driving force
- typical cell has high K+ inside
- Bulk electroneutrality says each K+ has a negative counterion
- K+ channels open, they travel down their gradient outside the cell
- K+ separated from their counterion
- electrical potential energy increases across the membrane until it’s equal and opposite to the chemical potential energy
- membrane voltage where equilibrium occurs is Nernst potential
How do you calculate the Nernst potential for an ion knowing extra and intracellular concentrations?
Vm (Vin-Vout) = Ex = -RT/zF (ln [X]in/[X]out)
How does net electrochemical driving force determine the direction of ion movement through a membrane?
Driving force = Vm - Ex
when DF < 0, cations enter the cell, anions exit
when DF > 0, cations exit cell and anions enter
What is the role of the Na-K-ATPase pump in establishing gradients of sodium and potassium?
pumps 3 Na+ out, 2 K+ in using ATP
1. Na+ in
2. ATP hydrolyzed, closing pore
3. extra pore opens, Na+ released
4. K+ binds
5. P lost, closing pore
6. ATP binds, K+ released
ouabain poisons ATPase
How are voltage differences across membranes produced?
selective ion permeability
- movement of small # of molecules produces a large change in V
ΔV = Q/C
How do secondary active transporters use energy stored in concentration gradient to drive movement of other molecules?
- co-transporters: 2Na/Glucose enter together; harness the electrochemical potential of certain ions (Na) to drive influx of other solutes against concentration gradients
- exchangers: 3Na/Ca exchanger; energy of Na gradient to drive Ca out of the cell
Why can a cell attain a Vm between -100 mV and +130 mV depending on permeability of the membrane?
the cell has different types of channels in different amounts; the Vm is determined by averaging the contributions of all ions
How do you calculate the flux of ions from GHK equation?
J = P x (Cout-Cin) /Δx
J = Pk (Ckout-Ckin) + Pna (Cnaout-Cnain) + ….. / Δx
Describe voltage-gated K+ and Na+.
K+: resting state (inside closed), open active state (slow, repolarization)
Na+: resting state (outside closed), active state (fast), inactivated state (slow, inside closed)
What are the phases of the AP?
- Below threshold (< -50 mV), all channels closed, at Vm
- Depolarization: (-50 mV to +30 mV): stimulus raises above -50 mV, Na+ channels open and K+ triggered (delay)
- Repolarization: (+30 mV to -70 mV): plateau, Na+ channels inactive, K+ channels open
- Hyperpolarization: slow closing of K+ channels
Compare and contrast the differences in outcome for graded and action potentials.
graded potentials: local triggering events cause gated channels to open, creating local change in Vm
- can be depolarizing or hyperpolarizing
- stronger stimulus produces larger GP
- spread is limited along membrane because current leaks/charges disperse
- can trigger AP if intense or long enough
Describe molecular basis for action potential’s all or none, non-decremental, and capable of propagation.
All-or-none: Once the threshold is reached, voltage-gated Na⁺ channels open fully, triggering a complete action potential
Nondecremental: shape and magnitude is constant along the membrane; delay between stimulus and response increases with distance
Propagation:
- An action potential triggers automatic propagation in excitable cells
- In contiguous conduction, local current spreads to neighboring sites, triggering new action potentials.
- Local current loops could initiate action potentials in both directions.
- Refractory periods prevent new action potentials, ensuring one-way propagation in nerves.
How does the AP propagate?
myelinated axon: current passes through Nodes of Ranvier quickly where Na/K channels are concentrated for APs; reduces leakage of current
What is the difference between absolute and relative refractory periods?
absolute: second response is not possible (entire portion above threshold) because Na+ channels are open or inactive
relative: second response is possible if strong stimulus (below threshold + hyper); K+ channels open
Describe spatial and temporal summation in the neuron.
spatial: inputs from multiple different neurons amplify signal
temporal: same axon fires multiple times
Differences between electrical and chemical synapses
Electrical: signals directly propagate from one cell to another through gap junctions, fast transmission, synchronized activity (cardiac + smooth muscle)!
Chemical: signal transmitted with neurotransmitters released into synaptic cleft, slower, unidirectional, more modulation
Steps of NT release into synaptic cleft?
- NT synthesized and packaged into vesicles at axon terminus
- AP arrives at the presynaptic terminal
- V-gated Ca2+ channels open and Ca2+ enters
- Rise in Ca2+ triggers fusion of synaptic vesicles with the presynaptic membrane
- NT diffuse across the synaptic cleft and bind to receptors on the post synaptic cleft
- Bound receptors activate postsynaptic cell
- NT broken down by acetylcholinesterase, is taken up by the presynaptic cleft or other cells, or diffuses away
ionotropic vs. metabotropic receptors and how they function in synapses?
ionotropic: directly opens with 2 ACh binding, allowing ions to flow through and depolarize membrane; fast!
- muscle contraction
Ex) Nicotinic AChR + serotonin (cations)
DEPOLARIZE (excitatory postsynaptic potential)
metabotropic: GPCRs activate G-protein that triggers intracellular signaling pathway (second messengers like cAMP); slow
- decrease HR
Ex) Glycine, GABA (anions)
HYPERPOLARIZE (inhibitory postsynaptic potential)
