Transporters and Membranes

By Sushil Pal

Slides made using WMS transporters lecture, Molecules

Contents

• Transports– Types– Properties– Regulation– Function– Key examples (in my opinion)

• Membrane Potentials

Transport types?

• Diffusion• Passive• Active• Co-transport

Examples….Diffusion

Passive Glucose transporter

Active ATPases (Ca++, Na+/K+, H+/K+)

Co-transport Symporters (Na+/glucose, Na+/Cl-, Na+/HCO---)Antiporters (Na+/H+, Na+/Ca++)

Properties of Transporters

• Transporters are integral membrane proteins.• Transporters are channels or carriers….

– What is the difference between these?

• Transporters are specific (or selective)…– What ways are they specific/selective?

• Transporters are regulated.• Transporters are passive or active

The effect of Transporters on physiological processes…??

• Uptake of metabolites.• Extrusion of waste products.• Maintenance of intracellular pH.• Generation and use of ion gradients.• Regulation of cell volume.

Transporter regulation…??

• Voltage gated – membrane potentials• Ligand gated – neurotransmitters – Ach• Mechanically gated – sound, touch

Passive and Active transport differences…?

• Passive– No metabolic energy use– Down a concentration gradient– Eg. Na+ entry into cells during AP

• Active– Metabolic energy use - ATP– Against a concentration gradient– Eg. H+ movement in electron transport chain

Important passive transporters..

1) GLUT– Function: move and trap glucose into cells

2) Cl-/HCO3- anion exchanger– Function: regulate pH– Found in erythrocytes

Important Active Transporters

• Plasma membrane Ca2+-ATPase.• Sarcoplasmic/endoplasmic reticulum Ca2+-

ATPase – for 2ndary messengers • Plasma membrane Na+:K+-ATPase• Plasma membrane H+:K+-ATPase – parietal

cells – acidic environment

Co Transporters

Co-transport systems

Symport AntiportUniport

• Found in many locations to help different cellular functions

• Do you know any co-transporters..?

• Na+ symporters• Glucose uptake (small intestine and kidney).• Amino acid uptake (luminal epithelial cells).• Cl- uptake (epithelial cells in small intestine).• HCO3

- uptake (regulates cell pH in many cell types).

• Na+ antiporters• H+ export (regulates cell pH in most cell types).• Ca2+ export (muscle cells).

• Na+-dependent anion exchanger• Na+ & HCO3

- influx and H+ & Cl- efflux

Ion concentrations

• I recommend learning these..

Ion concentrations in a typical cell

[K+]160 mM

[K+]5 mM

[Na+]10 mM

[Na+]150 mM

[Cl-]5 mM

[Cl-]115 mM

[Ca2+]

0.2 M[Ca2+]2 mM

[A-]165 mM

[A-]40 mM

Most organic moleculesare negatively charged.

-

-

-

-

-

-

-

-

+

+

+

+

+

+

+

+

Membrane potential = -70 mV

Nernst equation..simplified

• You should learn this too and know what the value means.– Your group work will run through more examples

than your lecture

Simplified Nernst equation at 37°C

Eion

61 mV

Zlog

[ion]out

[ion]in

=

Using the Nernst equation for K+ at 37°C

Eion

61 mV

Zlog

[ion]out

[ion]in

=

EK

61 mV

1log

5 mM

160 mM=

EK -91.8 mV=

If [K+]out increases to 10 mM (hyperkalaemia), Ek is –73 mV.Can result in ventricular arrhythmia and fibrillation.

Note: normal K+ con is 5mM outside the cells

Therefore an increase in extracellular K+ concentration will bring the membrane potential closer the threshold meaning the Action Potential will be easier to fire thus fibrillation and arrhythmias

Learn the action potential process!!

• Ie which channels are involved, what moves in and out etc

• It has come up in exams!!

Membrane potential• Depolarisation is a decrease in membrane potential.• Cytoplasmic side of the membrane becomes LESS negative

ie close to 0• Opening Na+ (or Ca2+) channels depolarises cells.

– Na+ (and Ca2+) ions flow into the cell.

• Hyperpolarisation is an increase in membrane potential.• Cytoplasmic side of the membrane becomes MORE

negative ie further from 0• Opening K+ or Cl- channels hyperpolarises cells.

– K+ ions flow out of the cell, Cl- ions flow into the cell.

Refectory Periods..

• Which types are they?• Why are they important?

Refractory periods

Membranes are refractory to stimulation during the action potential. This is the absolute refractory period.The membrane becomes more responsive as it repolarises. Very strong depolarisation produces a second action potential. This is the relative refractory period.

+60

+20

0

-20

+40

-40

-60

-80

Mem

bran

e po

tent

ial (

mV

)

1 2 3 40

Time (ms)

Absolute Relative refractory period

• Learn all the different types of transporters and channels in your lectures.– As the year goes on you will come across them

again and again so learning them in context will be more useful than in isolation.

• Getting you head around membrane potential is useful in Semester 2

Advice

Any questions??