Formative Questions Flashcards
Give TWO ways that a membrane protein may interact with the
hydrophobic domain of a membrane bilayer
• Transmembrane sequence of approximately 20-22 amino acids with
hydrophobic R-groups (often folded into α-helical structure, could be
multiple α-helices or rolled-up β-sheet, e.g. bacterial porins)
• Lipid-linked proteins through the insertion of the hydrophobic lipid
moiety (e.g. post-translational modification with fatty acid
(palmitoylation, mystriolation), e.g. G-proteins) )
Why do patients with Hereditary Spherocytosis become anaemic?
• Reduced levels of spectrin (most commonly), ankyrin (hereditary
elliptoidosis) or other cytoskeletal elements in heterozygotes
Results in weakened erythrocyte cytoskeletons
• Rounding up of erythrocytes, trapping in capillaries and cell lysis
(Clearance by the spleen)
Which of the following that can diffuse across biological
membrane bilayers without the aid of a transport protein or channel:
adenosine 5’ monophosphate adrenaline albumin carbon dioxide citrate ethanol glucose H+ Immunoglobulin Insulin Low density lipoprotein K+ Sucrose urea water
CO2
Ethanol
Urea
Water
In a cell, What is the the direction of the gradients (outwards/inwards) for Na+ and Cl-
For each, give approximate extracellular and intracellular
concentrations of the ion
Na:
In wards
Extracellular: (120?) 142-145
Intracellular: 10 - 12
Cl:
Inwards
Extracellular: 114 - 123
Intracellular: 3 - 4.2
Concentrations in mM
Gives some examples of:
a passive transporter that transports potassium ions
an active transporter that transports potassium ions
Passive transport:
Any potassium channel (voltage-insensitive, voltage-sensitive,
delayed rectifier, inward rectifier, ATP-sensitive (KATP), ROMK,
TWIK, TWEK, HERG, BKCa,SKCa)
Active transport: Na+/K+ATPase K+/Cl- cotransporter K+/H+ exchanger Na+/K+/2Cl cotransporter
How may a cell prevent cell shrinking.
Influx of Na, K or Cl to attract water osmotically
Name a drug or class of drugs that inhibits renal sodium
reabsorption
Name the transporter or channel inhibited by the drug
Give the kidney tubule location of the transporter
Loop diuretic
Na+/K+/2Cl cotransporter
(Thick) ascending limb (proximal tubule)
Thiazide
Na+/Cl- cotransporter
Distal convoluted tubule
Spironolactone
ROMK, Na+/K+/ATPase
Cortical collecting duct
Amiloride
Epithelial Na+ channel (ENaC)
Cortical collecting duct
What is the approximate resting membrane potential of a nerve cell
(neurone)
How is this resting membrane potential achieved?
-70 mV
Efflux of K+ ions through (voltage-insensitive) K+ channels
and minor inward leak of Na+ and Ca2+ ions
NOT Na/K/ATPase (although electrogenic, makes only a very
small contribution to resting membrane potential)
What would be the effect on membrane potential of activating:
nicotinic acetylcholine receptors
gamma aminobutyric acid receptors?
Depolarisation
Hyperpolarization
Concerning nerve action potentials:
what is meant by the term absolute refractory period?
explain why the absolute refractory period occurs
what property does the absolute refractory period confer on nerve
cells?
The absolute refractory period is the period during and immediately
following an action potential where it is impossible to stimulate the
membrane to re-fire an action potential (no matter how strong a
stimulus is applied).
The ARP occurs due to the inactivation of Na action potential.
(Further opening of Na occur until the channels have been reprimed by repolarisation of the membrane)
Prevents re-entrant excitation
Directionality in impulse propagation
Explain the effect on the conduction of nerve impulses of demyelination of a nerve fibre:
immediately after the loss of the myelin sheath?
after a period of recovery?
Conduction failure due to increased neuronal membrane
capacitance and current leak preventing nodally distributed channels from being raised to threshold
Re-establishment of nerve impulses with slower conduction velocity
due to the redistribution of nodal ion channels in the nerve
membrane (effectively becomes an unmyelinated nerve)
Explain the difference between homologous and heterologous
desensitisation in response to agonist binding to receptors
Homologous desensitisation – the process by which only the signal
from the stimulated receptor is reduced.
Heterologous desensitisation – the process when receptors for several
agonists become less effective even when only one has been
continuously stimulated.
Indicate TWO main mechanisms for drug elimination from the body
and, for each, indicate the tissue in which the mechanism occurs.
LIVER:
Oxidation by cytchrome P450 system
Conjugation to hydrophilic chemicals/sugars/glucuronidation
both of the above to increase the solubility of a drug to permit passage in the circulation & glomerular filtration
KIDNEY:
Glomerular filtration
In the signaling pathway from α1 adrenoceptor activation to the release of Ca2+from intracellular stores:
i. describe the mechanism for the stimulation of effector in response to
receptor activation in the plasma membrane.
ii. Explain how effector activation results in Ca intracellular stores
i. The receptor conformational change on agonist binding results in a
conformational change in the associated G-protein, Gq, resulting in
the release of GDP, binding of GTP
GαGTP.βγ dissociates and GαGTP diffuses in the plasma
membrane bilayer to activate the effector phosphatidylinositol 4,5-
bisphosphatase or phospholipase C (PLC)
ii. PLC releases inositol 1,3 5-trisphospate (IP3) from
phosphatidylinositol 4,5-bisphosphate (PIP2) as a second messenger within the cytoplasm
Binding of IP3 to IP3 receptors on the endo(sarco)plasmic reticulum
results in opening of ligand-gated Ca2+channels and release of
stored Ca2+
(released Ca2+ feeds back positively onto ryanodine receptors
(RyR) to stimulate Ca2+ induced Ca2+release)
What are the receptor subtypes for the following tissues & physiological responses:
Airways smooth muscle
Dilatation
Sinoatrial node
Negative chronotropy
Heart Ventricle Positive ionotropy (force)
Glands
Stimulation of glandular secretions
Beta 2
M2
Beta 1
M3 (some M1)
