All Content Flashcards
How fast are action potentials
Action potentials can travel at up to 120 m/s triggering at the nerve terminal, the release of neurotransmitters
What is the function of neurotransmitters?
Neurotransmitters carry the signal across the synaptic cleft. From the pre-synaptic neuron to the post-synaptic effector cell
What are the 5 steps of neurotransmitter release?
- Synthesis of Transmitter
- Storage in vesicles
- Release
- Activation of Post-Synaptic Receptors
- Inactivation
What happens in the release state of neurotransmitter release?
Action potential comes down to nerve terminal, where they are densely expressed voltage gated calcium channels. Depolarisation caused by action potential opens the calcium channels, calcium funnels into the nerve terminal, which is essential in causing the coordinated release or exocytosis of transmitter from the vesicles
How can drugs enhance synaptic transmission directly?
Direct stimulation of post synaptic receptors by
1. the natural transmitter
2. analogues - compounds that interact/activate the receptor
How can drugs enhance synaptic transmission indirectly?
Indirect action via
1. increased transmitter release
2. inhibition of transmitter removal
How can drugs inhibit synaptic transmission?
- Blocking synthesis, storage or release from the pre synaptic neurone
- Blocking postsynaptic receptors
What are agonists?
drugs, hormones, or transmitters which bind to specific receptors and initiate a conformational change in the receptor resulting in a biological response
What does affinity mean?
The ability to bind to receptors
What does efficacy mean?
the ability of an agonist, once bound to a receptor, to initiate a biological response
How do agonists work and what do they possess?
Agonists bind to receptors and activate them
Agonists possess both affinity and efficacy
How do antagonists work and what do they possess?
Antagonists bind to receptors but do not activate them
Antagonists possess affinity but lack efficacy
Antagonists block receptor activation by agonists
How do competitive antagonists work?
Competitive antagonists competes with the agonist for the “agonist binding site” on the receptor
Block is reversed by increasing agonist concentration
What are the 2 classes of cholinoceptor?
Nicotinic cholinoceptors - activated by ACh or the tobacco alkaloid nicotine but not by muscarine
Muscarinic cholinoceptors - activated by ACh or the fungal alkaloid muscarine but not by nicotine
How do you calculate Quantal Content?
mean EPP amplitude / mean MEPP amplitude
How does tetrodotoxin work?
Blocks Na+ channels (no action potential - no release, no EPP)
How does Conotoxins work?
Voltage gated Ca2+ cannels blocked (decrease Ca2+ influx - decreased release)
The EPP amplitude decreases; no change in the MEPP amplitude. A decreased quantal content
How does Dendrotoxin?
Dendrotoxin blocks voltage gated K+ channels - prolonged action potential
Increased Ca2+ influx - increased release
Increased epp amplitude; mepp amplitude - no change. Quantal content Increased
How does botulinum toxin work?
Blocks vesicle fusion by cleaving a vesicular protein for exocytosis - decreased release
EPP amplitude decreases, MEPP no change. Quantal content decreases
What is tubocurarine and what does it do?
Competitive non-depolarising neuromuscular agent
Muscle block reserved by anticholinesterases e.g. Neostigmine
What is alpha-bungarotoxin and what does it do?
Component of the venom of the Taiwan banded krait
Binds irreversibly to the agonist recognition site on the nicotinic receptor of the skeletal neuromuscular junction
Decreases the amplitude of both the epp and the mepp, with no effect on quantal content
irreversible and not reversed by neostigmine
What are the two functional parts of the Skeletal System?
Axial skeleton - Head, neck and trunk
Appendicular skeleton - Limbs and girdles
What are the types of bones?
Flat bones - protective
Long bones - tubular
Sesamoid bones - develop in tendons
Irregular bones - complex shape
Short bones - Cuboidal
What is the structure of bone?
Periosteum and Endosteum - Fibrous connective tissue coverings of bone
Perichondrium - Fibrous connective tissue covering articular cartilage
Cortical bone - rigid outer shell
Trabecular bone - interconnected struts (trabeculae)
Medullary Cavity - hollow part of bone containing bone marrow
Fibrous Joints Classification
Bones united by fibrous tissue
Provides stability
Sutures, Syndesmosis and Gomphosis
Cartilaginous joints Classification
Primary - Synchondroses - temporary or permanent unions - covered by hyaline cartilage
Secondary - Symphyses - permanent unions by fibrocartilage
Synovial Joints Classification
Joint capsule spans and encloses joint
Lined by synovial membrane and articulacartilage
Filled with lubricating synovial fluid - mobility
Several different types
What are the different types of Synovial joints?
Pivot joints - rotation around axis
Hinge joints - permit flexion and extension
Saddle joints - permit flexion, extension, abduction and adduction
Ball and socket joints- movement in multiple axes and planes
Condyloid joints - permit flexion, extension, abduction and adduction
Plane joints - sliding movements
What are ligaments?
Connect bone to bone
Fibrous bands of dense regular connective tissue
Stabilise articulating bones and reinforce joints
In musculoskeletal system classified into - capsular ligaments, intracapsular ligaments and extracapsular ligaments
What does skeletal muscles attach to?
Most skeletal muscles are attached directly or indirectly to bones, cartilage, ligaments or fascia, or to a combination of structures
Some attach to organs (eyeball), skin (facial muscles), mucous membranes (tongue muscles)
Organs of locomotion
Provide support and form, and heat
What is skeletal muscle?
Individual cells cylindrical with multiple elongated nuclei located peripherally
Cytoplasm has alternating dark and light bands (striations) - overlapping bands of contractile tissue (actin and myosin)
Muscle cells = muscle fibres
Tens or hundred of muscle fibres bundled together = fascicle
Skeletal muscle classification
Pennate - fascicles attach obliquely - unipennate, bipennate or multipennate
Convergent - arise from a broad area and converge to form a single attachment
Circular or sphincter - surround opening - constrict when contracted
Fusiform - spindle shaped with thick round bellies and tapered ends
Flat - parallel fibers
What are tendons?
Connect muscle to bone
Dense regular connective tissue
Transmits mechanical forces
What are the three types of contraction?
Reflexive - automatic e.g. diaphragm
Tonic - muscle tone - posture
Phasic
What are the two main types of phasic contraction?
Isotonic contractions - muscle changes length - two types - concentric (shortening) and eccentric (lengthening)
Isometric contractions - muscle length remains the same
What is the primary function of muscle?
Generate force or movement in response to a physiological stimulus - all muscles transduce a chemical or electrical signal into a mechanical response
Skeletal muscle contracts in response to neuromuscular synaptic transmission
A skeletal muscle fibre has a single NMJ where ACh receptors are concentrated
ACh released from the presynaptic nerve terminal binds to the nicotinic ACh receptors at the NMJ - receptors are non selective cation channels that open in response to ACh binding, resulting in a depolarization of Em known as an end plate potential - if the epp exceeds threshold for activating V-gated Na+ channels, an AP is generated
Generation of an AP initiates the sequence of events leading to contraction - ACh is rapidly inactivated by ACh-esterase
Levels of organisation in a skeletal muscle
Whole skeletal muscle (organ) - muscle fibre (a single cell) - myofibril (a specialised intracellular structure) - thick and thin filaments (cytoskeletal elements) - myosin and actin (protein molecules)
Skeletal muscle fibres are striated by a highly organised internal arrangement
A single, skeletal muscle cell (muscle fibre) is relatively large, elongated and cylinder shaped - 10-100 micrometers in diameter and up to ~75 cm in length
Myofibrils - specialised contractile elements that extend the entire length of the muscle fibre - muscle fibre can contain 100s to 1000s of myofibils
Each myofibril consists of a regular arrangement of cytoskeletal elements - the thick and thin filaments - Thick (special assemblies of the protein myosin) - Thin (made up primarily of the protein actin)
Troponin
Heterotrimer - Troponin T binds to a singe molecule of tropomyosin - Troponin C bind Ca2+ - Troponin I binds to actin and inhibits contraction
Each heterotrimer of troponin interacts with a single molecule of tropomyosin, which in turn interacts directly with 7 actin monomers
What do thick filaments consist of?
Composed of multiple myosin-II molecules
Each myosin-II molecule is a double trimer composed of - 2x intertwined chains - 2x regulatory chains - 2x alkali (or essential) light chains
What are the two heavy chains made up of in relation to thick filaments?
3 regions - tail, hinge and a head
Tail regions are alpha helices that intertwine
Hinge region the molecule opens to form 2 globular heads
Head regions (aka S1 fragments) are the cross-bridges between the thick and thin filaments of the sarcomere
What do the heads of heavy chain possess in relation to thick filaments?
Possess a binding site for actin and a site for binding and hydrolysing ATP
What complex is formed with the head portions of each myosin in relation to thick filaments?
Forms a complex with 2 light chains, 1 alkali and 1 regulatory
The alkali light chain stabilises the myosin head region
The regulatory light chain regulates the ATPase activity of myosin. The activity of this chain is regulated via phosphorylation by kinases
Muscle contraction
Muscle contraction is a cycle in which myosin-II heads bind to actin, these cross-bridges become distorted, and finally the myosin heads detach from actin
Energy for this cycling comes from the hydrolysis of ATP
In all 3 muscle types, an increase in intracellular Ca2+ concentration triggers contraction by removing the inhibition of cross bridge cycing
Upon stimulation the intracellular Ca2+ concentration ma rise from its resting level of less than 10^-7 M to greater than 10^-5 M
The subsequent decrease in intracellular Ca2+ concentration is the signal to cease cross-bridge cycling and relax
Role of Ca2+
Ca2+ modulates contraction via regulatory proteins rather than interacting directly with the contractile proteins
In the absence of Ca2+, these regulatory proteins act together to inhibit actin-myosin interactions, thus inhibiting the contractile processes
When Ca2+ bind to one or more of these proteins, a conformational change takes place in regulatory complex that releases the inhibition of the contraction
