1. Membrane transport Energy driven pumps
Chemiosmotic coupled transporters
Solute control

2. ATP driven pumps P-type ATPase F0F1 Energy efficient = reversible
Cation exchangers
Ca2+/H+
Na+K+
H+/K+
F0F1 H+
ATP synthesis
Energy efficient = reversible
ABC transporters
Nonionic species – peptides, drugs
CFTR – Cl-

3. P-type, E1-E2 Pump ATP-driven calcium pump
SERCA, NaK, HK, heavy metals
Ca2+, Na+, H+ out of cytoplasm
Staged ATP release E1
E1-ATP-2Ca
E1P-ADP-2Ca
SERCA structure
E E2 E2
E2P
E2P-2Ca

4. F0F1 pump Rotary protein complex V1-ATPase F1-ATP synthase
H+ out of cytoplasm
Mostly into vesicles
F1-ATP synthase
Mitochondria
High energy H+
Low energy H+ H+ H+
Proton Gradient
ADP
ADP H+ H+
ATP
ATP

5. ABC Transporters esp. prokaryotes Heterotetramer 2 ATP per cycle
Peptide uptake
Toxin emission
Locher et al., 2002

6. Transporter regulation
Phosphorylation
InsulinPKC/srcNaK activity
Ions
Mg2+, Mo2+..
Accessory proteins
NoradrenalinePKA--|phospholamban--|SERCA
Substrate concentrations
Mass action

7. Non-ATP powered transporters
Energy sources
Own concentration gradient (uniporter)
Other gradient
Symporter
Antiporter
Chemical modification
Released molecule different than adsorbed
Major facilitator
Transport
Group

8. Uniporter Glucose transporter GLUT1/GLUT4 Not a pore
Ligand mediated conformational change
Bi-directional, slow vs true channel
Glucose uptake in high-glucose
Glucose release in low glucose
Inhibited by actin filament disruption
Lachall et al., 1996

9. Antiporter NHE Na+/H+ exchanger Bistable proteins
High Na+ gradient (15 kJ/mole)
Proton efflux, pH control
Bistable proteins
Opposing openings
Substrates stabilize one or the other facing
Transition energy > thermal

10. Symporter Na+/K+/2Cl- cotransporter
Electroneutral
Independent of equilibrium potentials
Solely concentration gradients
Major source of Cl- entry
Electrolyte & osmotic balance
Substrate binding stabilizes transitional conformation

11. MFS regulation
Membrane transport/sequestration
Phosphorylation

12. Blood homeostasis Volume/pressue homeostasis Composition homeostasis
Kidney function
Osmotic regulation
Hormonal regulation
Neural regulation

13. Mass flow in kidney NaK (P-type) Kleak, Cl (ion channel)
NHE (MFS antiporter)
NKCC, NGC, ATA (MFS symporter)
GLUT, AA (MFS uniporter)
Tissue interstium
Lumen Na
NKCC
NaK Na K K
Kleak
NHE Cl
Glucose
GLUT
Glucose
NGC H OH AA
HCO3
ATA AA AA Pi Ca
CO2
CBA Cl

14. Ion currents in kidney Asymmetric distribution of transporters
Diffusion on one side
Counter-diffusive movement opposite
ATPNa gradientglucose gradient
ATP Energy
Tissue interstium
Lumen Na
NKCC
NAK Na K
NHE
Kleak Cl
NGC
GLUT
Glucose
Glucose AA
ATA AA AA
Glucose Energy
Na Energy
AA Energy

15. Regulatory specifics Phosphorylation Transport Genetic
Cell shrinkage cAMPPKANKCC activity
Vasopressin  AVPR2GsNaK activation
AngiotensinAT2--|cAMPPKA--|NHE
Transport
EGF PI3KNHE3 internalization
Lumen pressureNHE internalization
AT2PLCCaMKIINHE externalization
Genetic
Aldosterone  NaK upregulation