MnR Flashcards
What is the function of a β2-adrenoceptor-selective agonist
β2-adrenoceptor-selective agonists (e.g.salbutamol, salmeterol) are used in asthma to reverse bronchoconstriction. The β2- adrenoceptor-selectivity of such agents limits possible cardiovascular side-effects (e.g. positive inotropic and chronotropic actions)
How does cholesterol decrease membrane fluidity at high temperatures and increase fluidity at low temperatures?
At high temperatures where increased random movement of the fatty acid side chains and hence increased fluidity would occur, cholesterol by its interaction with the phospholipid reduces the movement of the fatty acid side chains at a given temperature, thereby enhancing phospholipid packing and reducing membrane fluidity.
At low temperatures where phospholipids would normally pack together into the ‘crystalline form’ gel state and reduce membrane fluidity, cholesterol by intercalating with the phospholipid molecules reduces the ability to form ordered packed crystals and thereby increases membrane fluidity.
What is hereditary elliptocytosis?
a common defect is a spectrin molecule that is unable to form heterotetramers resulting in fragile elliptoid cells
Parasympathetic nerve terminals at neuroeffector junctions, i.e. ‘presynaptic receptors’
Predominant receptor subtype?
Major Physiological action?
Predominant receptor subtype?
M2
Major Physiological action?
Feedback inhibition of neurotransmitter ACh release
List 3 histological features of skeletal muscle
Multiple nuclei
Nuclei along striations
Striations
Mutations affecting the LDL-receptor
- Receptor deficiency. Mutations that prevent expression of LDL receptor.
- Non-functional receptor. No binding of LDL. Normal coated pits and internalization.
- Receptor binding normal. No internalization due to a deletion in the C-terminal of the receptor that makes the interaction with the coated pits. LDL-receptors are found distributed over the whole cell surface in these patients.
During the heartbeat, myocardial Ca2+ channels open and result in a substantial increase in Ca2+ permeability.
In which direction does the Ca2+ flow?
Inwards, down the electrochemical gradient.
What would happen to the membrane potential if there was an increase in the permeability of the membrane to K+ ions?
the membrane will hyperpolarise and the membrane potential will move closer to EK
Describe the effects of sympathetic and parasympathetic innervation on the eye
Innervation of the iris: The iris has radial and sphincter muscles.
Sympathetic stimulation causes contraction of the radial muscles and pupil dilation.
Parasympathetic stimulation causes contraction of the sphincter muscles and pupil constriction.
What is known of the distribution of ion channels in myelinated nerve?
Sodium channels are limited to the node of Ranvier. Potassium channels may be present in the node, but are also present in the paranodal region, immediately to the side of the node. Some authorities argue that these then prevent re-entrant excitation of the node by preventing action potential spread under the myelin sheath
What is the class of acetylcholine receptor found at the parasympathetic neuroeffector junction?
Muscarinic receptors are found at the parasympathetic neuroeffector junction.
What occurs during the generation of an action potential?
- depolarization to threshold triggers the opening of many voltage-gated Na + channels
- the influx of Na + produces the rapid upstroke of the action potential (membrane potential moves towards ENa )
- this depolarization causes inactivation of Na + channels and opening of voltage- gated K+ channels
- Na+ influx stops and the increased K+ efflux leads to repolarization (membrane potential moves towards EK )
- relatively little ions move and the Na/K ATPase is NOT involved in action potential repolarization
State the effect of parasympathetic and sympathetic innervation and the receptors that mediate the effects, on the sweat glands
Parasympathetic = stimulates secretion
Sympathetic = stimulates secretion
Receptor = α1, muscarinic
Give an example of an agent which interferes with the release of acetylcholine.
Botulinum toxin (a potent toxin released by the bacterium Clostridium botulinum) interferes with the process of Ca2+-stimulated exocytosis markedly inhibiting vesicle fusion and ACh release. Although Botulinum toxin is most often associated with poisoning, it does have a specific therapeutic usage, with local injection of the toxin being used in the treatment of certain muscle dyskinesias.
Explain the terms spatial summation and temporal summation
Spatial summation- increase in the number of motor units innervating a muscle fibre at one time
Temporal summation- increase in the frequency of action potentials from a single motor unit towards a muscle.
What are the two permitted modes of mobility of proteins in a lipid bilayer?
- Fast axial rotation.
- Fast lateral diffusion within the plane of the bilayer.
State the effect of parasympathetic and sympathetic innervation and the receptors that mediate the effects, on the SA node in the heart
Parasympathetic = decreases heart rate
Sympathetic = increases heart rate
Receptor = β1
What is the effect of increased parasympathetic discharge in the heart?
- In the heart, the sino-atrial node, atria and atrioventricular node receives parasympathetic innervation, whilst the ventricular muscle does not
- the predominant effect of increased parasympathetic discharge is to decrease the rate of contraction (negative chronotopy) rather than to affect the force of contraction.
- Although there is little parasympathetic innervation of vascular smooth muscle, airways and GItract smooth muscle is richly innervated.
State the effect of parasympathetic and sympathetic innervation and the receptors that mediate the effects on the uterus in a non-pregnant women
Parasympathetic = Parasympathetic fibres of the uterus are derived from the pelvic splanchnic nerves (S2-S4) and localised to the cervix
Sympathetic = relaxation
Receptor = β2
What is MS?
This is a disease of the immune system where myelin is destroyed in certain areas of the CNS. This can have dramatic effects on the ability of previously myelinated axons to conduct action potentials properly.
Sinoatrial node
Predominant receptor subtype?
Major Physiological action?
Predominant receptor subtype?
M2
Major Physiological action?
Decrease inrate of spontaneous depolarisation to generate action potentials. Negative chronotropy
What are first order pharmacokinetics?
Constant FRACTION of drug eliminated in unit time.
Rate of elimination increases as drug concentration increases.
Half life can be defined.
Describe what is meant by the term saltatory conduction
Saltatory conduction is the mode of conduction of the nervous impulse found in myelinated nerve fibres.
Saltatory means leaping or jumping conduction; the action potential is set up only at nodes of Ranvier and an active node (undergoing an action potential) raises the next resting node of Ranvier to threshold
State the effect of parasympathetic and sympathetic innervation and the receptors that mediate the effects on adipose tissue
Parasympathetic = None
Sympathetic = stimulates lipolysis
Receptor = β3
Describe how the erthyrocyte cytoskeleton is structured, and which components are disturbed in hereditary spherocytosis.
The erythrocyte cytoskeleton is a network of spectrin and actin molecules. Spectrin is a long, floppy rod- like molecule. α1 and β1 subunits wind together to form an antiparallel heterodimer and two heterodimers then form a head-to-head association to form a heterotetramer of α2β2. These rods are crosslinked into networks by short actin protofilaments (~14 actin monomers), and band 4.1 and adducin molecules which form interactions towards the ends of the spectrin rods. The spectrin-actin network is attached to the membrane through adapter proteins. Ankyrin (band 4.9) and band 4.1 link spectrin and band 3 protein and glycophorin A, respectively. Attachment of integral membrane proteins to the cytoskeleton restricts the lateral mobility of the membrane protein.
Name the mechanisms which transduce an extracellular hydrophilic signal into an intracellular event.
- Membrane-bound receptors with integral ion channels
- Membrane-bound receptors with integral enzyme activity
- Membrane-bound receptors which couple to effectors through transducing proteins
- Intracellular receptors for hydrophobic ligands
Which noradrenalin receptor is found in the ventricles?
β1
What type of fibre arrangement does the bicep have?
Fusiform
The erythrocyte cytoskeleton is a network of what?
Spectrin and actin molecules.
What determines whether a nerve terminal is “dopaminergic” (releases dopamine) or “noradrenergic” (releases noradrenaline)?
- The first two enzymes in the pathway – tyrosine hydroxylase and DOPA decarboxylase – are both cytosolic
- whereas the enzyme which converts dopamine to noradrenaline – dopamine β-hydroxylase – is present within the synaptic vesicles.
Name the TWO major enzymes responsible for inactivation of noradrenaline?
Monoamine oxidase (MOA)
Catechol-O-methyl transferase (COMT)
What are the consequences of increasing parasympathetic tone in the eye? Might this be beneficial in decreasing intraocular pressure?
- Increased parasympathetic tone causes contraction of the sphincter muscle of the iris, narrowing the pupil.
- This improves drainage of the aqueous humor by relieving folding of the iris over the canal of Schlemm.
- This alleviates raised introcular pressure in glaucoma.
- This effect can be mimicked by muscarinic agonists such as pilocarpine, which is used clinically.
State the effect of parasympathetic and sympathetic innervation and the receptors that mediate the effects n the bladder wall.
Parasympathetic = Contraction
Sympathetic = Relaxation
Receptor = β2
What are the 5 general functions of biological membranes?
- Continuous highly selective permeability barrier.
- Allows control of the enclosed chemical environment
- Communication - control the flow of information between cells and their environment
- Recognition - signalling molecules, adhesion proteins, immune surveillance
- Signal generation in response to stimuli - electrical, chemical
What unwanted side effects limit the usefulness of Muscarinic antagonist?
- Decreased secretion: Salivary, lacrimal, bronchial and sweat gland secretions are inhibited, even at very low doses of muscarinic antagonists resulting in uncomfortably dry mouth and skin.
- Although at low concentrations muscarinic antagonists can cause a centrally-mediated paradoxical decrease in heart rate, higher doses cause the predictable mild tachycardia resulting from inhibition of resting vagal tone.
- Through effects on muscles of the urinary tract, muscarinic antagonists can cause urinary retention, particularly in the elderly.
- Central effects of muscarinic antagonists are perhaps the factor which most limits the utility of this class of agent. Thus, even at low doses, a muscarinic antagonist which can enter the brain will cause restlessness
Apart from glucose, what other metabolites use the sodium gradient for their uptake into cells against the concentration gradient?
Amino acids. There is a family of known transporters for different groups of related amino acids
