Phys-Pharm Flashcards
Cell Membrane Composition (by weight)
42% lipids
55% proteins
3% carbohydrates
Intracellular Concentrations of Ions
K+ 140mM
Na+ 5-15mM
Cl- 4mM
Ca2+ 0.0001mM
Extracellular Concentrations of Ions
K+ 5mM
Na+ 145mM
Cl- 110mM
Ca2+ 2.5-5mM
transport across the membrane
diffusion (lipid soluble molecules)
transport via transport molecules (small molecules + ions)
endocytosis (large molecules)
Active vs Passive Transport
Active transport uses ATP directly (sets up gradients)
Passive Transport uses ATP indirectly (uses gradients set up by Active transport)
Active Transport
ATPases and Pumps LOW TURNOVER (<100/sec)
Na+/K+ ATPase
Na+/K+ Pump ubiquitous tetramer (2 alpha-, 2 beta- subunits) 3 Na+ out of cell, 2 K+ into cell maintains low intracellular Na+ Conc. Requires ATP (ATP hydrolysis)
Passive Transport
Pores (aquaporin) tend to always be open
Channels (Na+ Channel) allow ions through
Carriers (Sodium Glucose Carrier) allows ions and molecules through via a conformational change
Carriers Classification
Uniporters - Move one solute
Symporters (Cotransporter) - Move more than one solute in the same direction
Antiporter (Exchanger) - Move more than one solute in opposite directions
Carriers
Facilitated diffusion + electrodiffusion
Turnover = 10^2 to 10^3 /sec
highly selective
can demonstrate saturation
Carrier Saturation
When all carriers are moving the maximum number of ions it demonstrates saturation
Ion Channels
Set Membrane Potentials
Gated (open gate = conductive and ions flow making a current, closed gate = non conductive and ions don’t flow meaning no current)
HIGH TURNOVER = 10^6 to 10^8 / sec
Na+,Cl-,K+,Ca2+ non-selective
Patch Clamp Technique
Measures current from ion channels 2 types Cell Attached (electrode is sealed onto membrane, looks at ion channel directly) Whole Cell (electrode is inserted into cell, current is recorded from all ion channels in the cell)
Equation for total current in cell
I = N.Po.g(Vm-Ei) . N is number of channels. Po is open probability. g is single channel conductance. Vm is membrane potential. Ei is nernst potential of ion I (equilibrium potential).
Membrane Potentials
In all cell membranes
Usually negative
functionally vital - mediated transport of ions
Measuring Vm
Measured Intracellularly
Narrow, sharp, glass electrode pushed into cell through membrane
Electrical contact between KCl in electrode measures Vm compared to air outside
Contribution of Na+/K+ ATPase to Vm
Contributes 20%
Indirect contribution intracellularly
Contribution of K+ Channels
High IC conc, Low EC conc
K+ moves to EC generating -ve Vm
-ve membrane potential brings K+ back into the cell
movement out=movement in - no net flow = no current
Equilibrium Potential Equation
Eion=RT/zF x Ln([ion]o/[ion]i)
OR
Eion=61.5/z x log([ion]o/[ion]i)
Eion = equilibrium potential R = gas constant T = temp in K z = valence ion F = faradays constant
Equilibrium Potential
When no net movement of an ion
Vm=/=Eion because there’s multiple channels
Contribution of Na+ Channels
High EC conc, low IC conc
+ve membrane potential pushes Na+ out of the cell
movement out = movement in so no current
When balanced = ENa
but Vm=/=ENa because some sodium channels are closed
Goldman Equation
Vm=RT/zF x ln(PNa[Na]o+PK[K]o)/(PNa[Na]i+PK[K]i)
or
Vm=61.5/z x log(PNa[Na]o+PK[K]o)/(PNa[Na]i+PK[K]i)
Electrogenic Transport
Leads to the translocation of net charge across the membrane.
Change in Vm = Change in permeability
Why control intracellular pH
If pH changes, change in protein charges, change in protein conformation, change in function, can be a disaster.
Control of intracellular pH
increase [H+] = acidify
compensate by removing H+ (alkalisation)
decrease [H+] = alkalinise
compensate by adding H+ (acidification)
Measuring Intracellular pH
insert 2 electrodes into cell, measure voltage difference change in voltage is proportional to change in pH (electrodes calibrated with pH standards) pH=(V-offset)/slope HARD TO USE IN SMALL CELLS
Measuring Intracellular pH
insert 2 electrodes into cell, measure voltage difference change in voltage is proportional to change in pH (electrodes calibrated with pH standards) pH=(V-offset)/slope HARD TO USE IN SMALL CELLS
