Integrated Physiology With Pharmacolgy

Question 1

Main intracellular cation concentrations

Answer 1

Low Na+ ~ 15mM
High K+ ~150mM
Rel higher Ca2+ ~10*-6 scale (more than outside cell)

Question 2

Main extracellular cation concentrations

Answer 2

High Na+ ~150mM
Low K+ ~5mM
Rel lower Ca2+ ~10*-9 scale

Question 3

Main transport protein classes and characteristics

Answer 3

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

Question 4

Measuring current on a cell

Answer 4

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

Question 5

Equation for measuring current flow on a population of ion channels

Answer 5

I = N * P0 * g * ( Vm * Ei )

Question 6

K+ ion distribution across the cell membrane

Answer 6

Chem gradient IN>OUT flow is IN->OUT

E gradient IN- OUT+ flow IN

Question 7

Na+ ion distribution

Answer 7

Chem gradient IN

Question 8

Benefit of Goldman equasion over Nernst in biological application

Answer 8

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

Question 9

How is the Na-K-Pump involved in establishing the membrane potential?

Answer 9

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.

Question 10

What other processes rely on the electrochemical gradient set up by the NaKPump

Answer 10

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

Question 11

What are receptors categorised by?

Answer 11

Structure
Signalling
Pharmacology

Question 12

Characteristics of ligand gated ion channels

Answer 12

4 transmem domains, binding domain, ion chan
When agonist bound chan open
Eg all classical neurotransmitter Rs (N2)

Question 13

What are GPCR characteristics

Answer 13

Most abundant in genome
7transmem, binding domain, G prot coupled
Eg MAchRs

Question 14

Characteristics of kinase linked Rs

Answer 14

Has a Kinase linked or attracts one
Single pass, binding domain
All ligands are proteins
Eg growth factor R, insulin R, antibody R

Question 15

Characteristics of nuclear receptors

Answer 15

In cytosol, have DNA binding domain, influence gene tanscription
All ligands lipid soluable
Eg steroid hormone R

Question 16

What is R specificity?

Answer 16

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

Question 17

Classes of ligands

Answer 17

Small peptides (abundant)
Biologicals: peptides

Question 18

What factors determine the occupation of a drug on a R?

Answer 18

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

Question 19

What determines activation of receptors

Answer 19

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)

Question 20

Which measurement is used to classify drugs?

Answer 20

Affinity, bc antagonists by default show no response and therefore no efficacy.

Question 21

What is occupancy and how it is measured

Answer 21

Proportion of Rs occupied / no of all Rs
on a 1-0 scale

Radioligand binding essay