Histology Flashcards
Name 2 neuroscientists that contributed greatly to the field.
(hint: technique + application)
- Camillo Golgi - discovered the silver-staining technique
- Santiago Ramón y Cajal: applied the technique all over the body to map the human nervous system
Their combined work gained them the Nobel Prize for Physiology & Medicine in 1906
What characteristic allows neurones to communicate and what do they use to do so?
The phospholipid belayer with ion channels produces an excitable membrane that allows neurones to communicate using ions (e.g. Na+, K+, Cl- & Ca2+).
This allows the presence of concentration gradients and electrostatic potentials.
What specialised synapses are present in tissues including the heart and connective tissue? What type of communication do they allow and what can go wrong here in a clinical setting?
Gap junctions (I.e. connexons) are electrical synapses present in these tissue that allow fast signalling and bi-directional communication. Certain disorders can affect these gap junctions including epilepsy, which is the result of uncontrolled activation of these.
Briefly described the dream of Otto Lowei and what is contributed to neuronal signalling.
Otto Lowei was a neuroscientist that had a dream that inspired him to investigate an important question in neuroscience - is there a chemical component involved in neuronal signalling? He took 2 frogs hearts and placed heart 1 in solution and stimulated the vagus nerve = heart slowing down. He then removed heart 1 and replaced it with heart 2. He noted that heart 2 also slowed down without the stimulation of the vagus nerve. This was proof that there was a chemical signal - first known as Vagusstuff but now acetylcholine (ACh).
n.b. Stimulation of vagus nerve = release of ACh = muscarinic receptor-complex = slows the heart
Stimulation of accelerans nerve = release of norepinephrine (NE) = beta2-adrenergic receptor complex = heart speeds up
What was Sir Bernard Katz major neuroscience discovery?
With research involving the motor end-plate and cholinergic transmission, Katz discovered that synaptic transmission is quantal.
Compare and contract excitatory and inhibitory electrical synapses.
Excitatory synapses: * Asymmetrical synapses * Gray’s type I * Rounded synaptic vesicles Inhibitory synapses: * Symmetrical synapses * Gray’s type II * Flattened/ pleomorphic synaptic vesicles
Out of the 4 possible synaptic apposition, what type is also inhibitory?
Axo-axonic
What are the 2 types of neurotransmitter receptors? (Incl. Brief explanation)
- Ionotropic - a pore is formed in the membrane and, once activated, undergoes a conformational change (I.e. opens and closes) to allow ions to pass across the membrane. It has relatively quick effects.
- Metabotropic - an example of this type of receptor is a G-protein coupled receptor which have much slower effects
Briefly describe synaptic plasticity and the neuro-components involved.
Synaptic plasticity refers to the changes that occurs at neuronal junctions and synapses that affects how efficiently neurones communicate. It has been linked to memory storage and how the brain changes and adapts to new information. There are 2 main receptor types involved in this functions: AMPA & NMDA.
- AMPARs are pentemric structures composed of 4 subunits (GluR1-GluR4). If a receptor includes the GluR2 subunit, it is impermeable to Ca2+.
- NMDARs are composed of a NR1 & NR2 subunit. These channels are impermeable to Ca2+ due to a magnesium block, which can only be lifted if the Em is below -30mV.
Briefly describe the process involved in Long-Term Potentiation (LTP).
LTP is thought to be the cellular process responsible for learning and memory. It is regarded as the ability of excitatory synapses to become more sensitive to specific NTs due to transmission patterns. Process =
1. AMPARs activated and K+ ions leave the cell and Na+ enters the cell = membrane depolarisation
2. Magnesium block removed (-30mV) = influx of Ca2+ ions into the post-synaptic membrane
3. Activation of Tyrosine-Kinase = NDMARs activation = Ca2+ increased conc.
4. Activation of CaMKii, which phosphorylates AMPARs = increases AMPARs activation = insertion of new AMPARs
= LONG TERM POTENTIATION
List the 6 steps involved in cell-to-cell communication.
- SYNTHESIS of the signalling molecule - the receptor will detect a response and the cell will synthesise a signalling molecule
- RELEASE of the signalling molecule
- TRANSPORT to the site of action (I.e. target cell)
- DETECTION of the signal by a specific receptor
- ALTERATION in cell function
- REMOVAL of signal and termination (I.e. receptor desensitisation)
Name the 3 types of signalling including examples.
- Autocrine: signal acts upon releasing cell (I.e. self-activation). Examples include epinephrine acting on alpha2-adrenoceptors to inhibit NT release
- Paracrine: soluble signals act upon an adjacent cell (e.g. ACh acting on skeletal muscle via a neuromuscular junction)
- Endocrine: signals act at a target cell distant from their site of synthesis (e.g. hormones - insulin)
Describe the actions of an Intracellular receptor and what type of molecules use this type?
Intracellular receptors are used by hydrophobic signalling molecular (e.g. steroid and thyroid hormones) that travel in the blood via a transport protein. Once the molecule has successfully crossed the plasma membrane, it binds to a cytosol receptor that trans locates to the nucleus and alters DNA via becoming a transcription factor.
What are the actions of plasma membrane surface receptors and what type of molecules use these?
Hydrophilic molecules (e.g. adrenaline, histamine) use surface receptors as they can not cross the plasma membrane but can travel freely in blood. Once they have bound to the receptor, they trigger Intracellular chemical responses (e.g. second messengers).
What type of skeletal muscle receptors use ACh and what effect does it have?
Nicotinic ACh receptors are found in skeletal muscle and, once activated, cause depolarisation which is a relatively rapid effect.
What chemicals can reduce the channel opening time of a nACHRs? Where do these chemicals bind on the receptor?
Certain anaesthetics including isofluorane, halothane and NO. These chemicals bind to the loop between the M2 and M3 subunits.
Explain the structure of a nicotinic AChR (nAChR) including subunit structure.
A nAChR has a pentemeric structure which a combination of alpha, beta, gamma and delta subunits. Each subunit contains
- an Extracellular N-terminus which holds the ACh binding sites (x2).
- 4 transmembrane alpha-helixes within the subunits named M1-M4.
- Glycosylation and disulphides bonds also confer stability of the receptor.
- Glu + Thr in pore provides electron pairs that attracts cations and excludes anions
What can be used to determine the direction of movement of an ion across a permeable membrane?
The Nerst Equation
What is the resting membrane potential (Em)?
Em is the voltage difference across a cell’s membrane at rest. It can be calculated by finding the difference between the voltage of the cytoplasm and ECM.
- Neuron = -70mV
- Muscle = -90mV
What types of channels maintain Em?
There are PASSIVE (leak) channels that are constantly open and also ACTIVE channels that open and close in response to a specific stimuli. There are 3 main types of active channels!
- Chemically-gated channel
- Voltage-gated channel
- Mechanically-gated channel
What are graded potentials?
Graded potentials are changes (either depolarising or hyperpolarising) in membrane voltage that is lost quickly due to the permeable plasma membrane. If a graded potential passes the threshold of membrane voltage an action potential can occur.
What is an action potential?
An AP is a rapid change in Em caused by rapid activation and fluxes of ion currents, followed by a return to resting Em. They are the basis of cell-to-cell communication.
What is ‘Saltatory Conduction’?
The propagation of an AP along an axon via Nodes of Ranvier (unmyelinated sections of an axon), which increases conductoin velocity of APs.
Is Epithelia vascular or avascular?
Avascular
Describe the two laminas of epithelium and their relation to the basement membrane.
Epithelium has two laminas:
1. Basal lamina: comprised of the lamina lucida and dense - collagen fibres
2. Reticular lamina: composed of reticular fibres
The combination of these two laminas creates the basement membrane of epithelium cells.
What are the 4 shape types of epithelium?
Squamous, cuboidal, columnar and transitional (used if the cell shape is difficult to classify).
Describe the histology of the inner lining of the cervix? What clinical observation can be seen here?
The inner lining of the cervix is composed of 2 different types of epithelium:
1. Glandular columnar cells - secrete mucus
2. Stratified squamous epithelial cells - protective function
Cervical cancer is a life-threatening disease that can occur in females and is diagnoses via the use of Pap tests. This method takes a biopsy of the cervical tissue and look for cell changes under a microscope. Any changes observed have occurred due to the presence of the human papilloma virus (HPV).
What 3 appearance can the apical surface of epithelium have?
- Smooth - reduces friction
- Folds - present in organs that need to change shape
- Specialisations -
a. Microvilli: an extension of the cytoplasm and formed by actin microfilaments. Act by increasing surface area and favour the absorption and movement of nutrients. Found in the small intestine as the ‘brush border’.
b. Stereocillia: closely related to microvilli but longer and thinner. They are essential for sensation and absorption. Found in the epididymis and sensory hair cells of the internal ear.
c. Cilia: these motility devices are comprised of tubulin (an outer ring of 9 and inner duo). They are found in the respiratory epithelium and Fallopian tubes.
What are the 3 major components of the cytoskeleton?
- Microtubules: large, hello tubes of tubulin that determine the cell’s shape
- Intermediate filaments: strong structures that stabilise the cell (e.g. keratin, desmin, vimentin).
Microfilaments: bundles of myosin or actin filaments that generate movement and provide mechanical support.
