Integrated Physiology With Pharmacolgy Flashcards
Main intracellular cation concentrations
Low Na+ ~ 15mM
High K+ ~150mM
Rel higher Ca2+ ~10*-6 scale (more than outside cell)
Main extracellular cation concentrations
High Na+ ~150mM
Low K+ ~5mM
Rel lower Ca2+ ~10*-9 scale
Main transport protein classes and characteristics
Active transport: ATP hydrolysis, electrochemical gradient independent; low turnover
Carrier mediated transport: electrochem gradient dependent; uni, sym, antiporter; reaches saturation at transport maximum, higher turnover
Channels: ion selective, gated, always conductive when open, >1 ion in chan; highest turnover
Measuring current on a cell
Patch clamp method: pipette on cell
Cell attached measures ion chans on pipette patch, on cell surface
Whole cell: measures all ion chan current flow, pierces cell membranes
Equation for measuring current flow on a population of ion channels
I = N * P0 * g * ( Vm * Ei )
K+ ion distribution across the cell membrane
Chem gradient IN>OUT flow is IN->OUT
E gradient IN- OUT+ flow IN
Na+ ion distribution
Chem gradient IN
Benefit of Goldman equasion over Nernst in biological application
Nernst doesn’t consider relative permeability, whereas Goldman does.
Membrane is ~50-75 times more permeable to K+ than it is to Na+ (1:75), which shifts the resting pot towards the Equilibrium pot [K+]: -70mV- -80mV
How is the Na-K-Pump involved in establishing the membrane potential?
Keeps the intracellular Na+levels low, therefore sets the gradient/ driving force.
On itself, the electrogenic transport (3kations for 2kations) only contributes 20% of the RP.
When the pump is blocked, the RP disappears ca over 20 min.
What other processes rely on the electrochemical gradient set up by the NaKPump
The generation of the AP: high driving force for Na+ -> at changed permeability Na stream in quickly; restored by perm closure and K+ chan opening
The Amino Acid Na+ cotransport: Na gets in using electrochem gradient, carries AA -> open K chan to restore modified pot
What are receptors categorised by?
Structure
Signalling
Pharmacology
Characteristics of ligand gated ion channels
4 transmem domains, binding domain, ion chan
When agonist bound chan open
Eg all classical neurotransmitter Rs (N2)
What are GPCR characteristics
Most abundant in genome
7transmem, binding domain, G prot coupled
Eg MAchRs
Characteristics of kinase linked Rs
Has a Kinase linked or attracts one
Single pass, binding domain
All ligands are proteins
Eg growth factor R, insulin R, antibody R
Characteristics of nuclear receptors
In cytosol, have DNA binding domain, influence gene tanscription
All ligands lipid soluable
Eg steroid hormone R
What is R specificity?
Rs are specific for a certain class of ligands, not just one This is why cross action is possible At maxed out conc of a specific ligand, it will start to interact with other Rs as well
Classes of ligands
Small peptides (abundant) Biologicals: peptides
What factors determine the occupation of a drug on a R?
Affinity is measured KD= k-1/k1 => backwards reaction / forward reaction => the smaller KD the larger the affinity
Eg the most likely to bind to R
What determines activation of receptors
Efficacy shows how good a ligand is at producing a response/ configurational change to ellicit an active state
Agonist is at 1 (100% likelyhood of response) antagonists 0 (no response)
Which measurement is used to classify drugs?
Affinity, bc antagonists by default show no response and therefore no efficacy.
What is occupancy and how it is measured
Proportion of Rs occupied / no of all Rs
on a 1-0 scale
Radioligand binding essay
