Cellular Mechanisms Flashcards
Kinase Linked Receptors Outline
Large single chain protein. Single membrane spanning helical region. Extracellular = binding domain, intracellular = variable function.
Kinase Linked Receptors Function
Immune response, cell division and cell differentiation
3 Kinase Receptor types
tyrosine kinases (eg nerve growth), serin/theroine kinase (eg growth factor) and cytosolic kinases (interacts with cytokine receptors with no enzyme activity eg interferons)
Growth Factor (serine receptor) Pathway steps
Agonist binding, (polymerization +) dimerisation, autophosphorylation and gene transcription
Autophosphorylation Def
Phosphate attaches to receptor from cytosol. Receptor doesn’t need phosphate applied from other receptors
Dimerisation Outline
Allosteric binding to receptor inducing confirmational change for more effective action
Cytokine Receptors Pathways Step
Receptor binding, dimerization, phosphorylation and gene transcription
Purpose of medicine
Pharmacological intervention. Maintain physiological functions (homeostasis).
Cell Types
Blood, muscle, bone, fat, nervous and sex
Cell Functions
Structure, growth, reproduction, apoptosis, metabolism, temp regulation, communication and material transport
Differences between juxtracrine and paracrine
Juxtracrine stimulate cells in contact with them. Paracrine cells stimulate cells close to them (but not necessarily in contact with eachother)
Apoptosis Def
Regulated cell death
Rapidly acting cell mechanisms (milliseconds to hours)
Excitation (changes in membrane potential), contraction (smooth and skeletal muscles) and secretion (chemical mediators - cytokines)
Slower acting cell mechanisms (days+)
Cell proliferation and apoptosis
Host Defence Response Acting Cell Mechanisms
Anti-inflammatories and immuno-therapeutics
How is short term cell mechanisms regulated
Stores and release of intracellular Ca^2+. Dependent regulation of functional proteins (enzymes, contractile and vesicle proteins)
Where Calcium is stored in cells
Sarcoplasmic Reticulum (muscle cells), Endoplasmic Reticulum, mitochondria, free Ca, extracellularly (1/50 the amount Ca free)
4 main routes that Ca enters cell
Voltage gated channels, ligand gated Ca channels, store operated Ca channels and Na+ - Ca^2+ exchange channels
Voltage Gated Ca Channels Outline
Ca^2+ enters cell when membrane depolarises. 5 types: L, T, N, P/Q and R
Ligand Gated Ca Channels Outline
Activated by excitatory neurotransmitters (eg GABA). Non-selective transports Ca^2+ and other cations
Store Operated Ca Channels Outline
Channels that open within the cell membrane when ER Ca levels are low. Not sensitive to cytosolic free Ca
Na+ and Ca^2+ exchange
Controlled Ca^2+-ATPases. Ca^2+ is pushed out so 3 Na+ ions can be pushed in
2 types of Ca channels in endoplasmic and sarcoplasmic reticulum
Inositol trisphosphate receptors (Ca influx) and Ryanodine receptors (Ca efflux)
Ionisotal Trisphosphate Receptor Outline
Gq-coupled receptors stimulated Ionisotal Trisphosphate. Results in increased Ca in ER and SR
Ryanodine Receptor Coupling
Excitation-contraction coupling in cardiac and skeletal muscles
2 ways in which Ca Mediates
Direct Binding or Binding to Intermediate Proteins
Examples of an intermediate protein
Calmodulin. This undergoes further protein interactions to effect gene interactions
Relationship between voltage required for channels and concentration gradient
The steeper the push up the con gradient = more voltage required
Excitability Def
Cell’s ability to regenerate an electrical response due to the depolarisation of it’s membrane as an action potential
Cells that respond to action potentials
Neurons, muscle, skeletal, cardiac, smooth and endocrine
Why might fluctuations of free Calcium differ from cell to cell
Due to different action potentials firing due to different resting membrane potentials
3 subcategories of muscle cells
Skeletal (sarcomeres, voluntary movement), cardiac (sarcomeres, involuntary heart beat) and smooth (no sarcomeres, involuntary airways, GIT, ect)
Association between Ca movement and contraction of muscle cells
Contraction is a result of increased Ca^2+ in all cells by stimulation of IP3
What process does cardiac and skeletal muscle have that smooth cells doesn’t
The binding of Ca to troponin when forming cross bridges. In smooth cells the troponin and tropomysoin molecules aren’t present so Ca converts myosin to myosin P
How does subutamol act in the treatment of asthma
Beta 2 (protein-kinase A) receptor antagonist. Binding results in a decrease in free cell Ca
Examples of endogenous (natural) chemical mediators
Neurotransmitters, hormones and inflammatory mediators
Relationship between Ca and Exocytosis
Vesicles only fuse to cell membrane, releasing contents when Ca influx has occurred at end of depolarisation
2 ways in which Ca influences diffusion of chemical mediators into synapse
Voltage gated Ca channels (rapid acting) and Intraceellular stores (slow acting (endocrine and exocrine glands)
