1. Cellular Homeostasis -APS Refresher Course “In the beginning … there was the cell” Michael F. Romero, PhD Depts. Physiology & Biophysics and Pharmacology Case Western Reserve University, Cleveland, OH
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2. glutamate dehydrogenase System/Organ Physiology
Levels of Homeostasis
nHCO3-
NBC1
Na+ H+
ATPase
3Na+
2K+
Blood
CO2
H2O
NHE3
gln
Glut
CA-2
Gln
Glu-
α-KG
glutaminase
glutamate dehydrogenase
2 NH3
2 NH4+
System/Organ Physiology I
Organism Physiology
Cell & Molecular Physiology

3. Genetic Control -nucleus
Cellular Structure
Genetic Control -nucleus
Question: How does the Cell “know” to organize & control cell functions?
Energy Control -mitochondria
Answer = Cellular Homeostasis
© Boron & Boulpaep (2003), Medical Physiology, Saunders

4. Agenda – Cellular Homeostasis post Genome(s)
8:00 – 8:10 In the beginning… there was the cell. M.F. Romero, Case Western Res. Univ.
8:10 – 9:00 Generation of membrane potential. S. Wright, Univ. of Arizona Col. of Med.
9:00 – 9:50 Cellular ionic homeostasis / channel-transporter physiology. G.R. Dubyak, Case Western Res. Univ.
9:50 – 10:00 Break / Coffee/ Tea
10:00 – 10:50 Cellular volume homeostasis. K. Strange, Vanderbilt Univ.
10:50 – 11:40 Cellular pH homeostasis. W.F. Boron, Yale Univ.
11:40 – 12:00 Final Discussion - All participants

5. Nernst Equation at Equilibrium:
8:10 Generation of membrane potential Steve Wright, Univ. of Arizona Col. of Med.
at Equilibrium:
Electrical Force = Chemical Force (electrical ‘voltage’ = chemical ‘gradient’)
VKzKF = -RT ln
[K+]in
[K+]out
Maybe lightning bolt for “electrical force”
Bubbling beaker/flask for “chemical force”
VK = ln
[K+]in
[K+]out
-RT
zKF
Nernst Equation

6. 25 Na+ 90 K+ 1e-4 Ca2+ 0.8 Mg2+ 35 Cl- 12 HCO3– 0.7 PO43- 0.7 SO42-
Mammalian Cell Gradients
Extracellular
25 Na+ 90 K+ 1e-4 Ca Mg Cl HCO3– 0.7 PO SO42-
Intracellular
Interstitial space
145 Na+ 5 K Ca Mg Cl HCO3– 1 PO SO42-
Vm ~ -60mV
Background: RGB = 255, 215, 175
Interstitial Fluid: RGB = 178, 220, 255
Cell interior: RGB = 169, 207, 161
Cell membrane: from left -> 5 down.
Cell membrane fill: 5 less than WHITE.
CA II fill: 3 less than WHITE.
Other Transporter fill: from right -> 2 up, 3 over
CO2 Icon fill: RGB = 203, 125, 164

7. Mammalian Cell Gradients
145 Na K Cl-
Extracellular
Interstitial space
Vm ~ -60mV
25 Na K Cl-
Intracellular
Na+ K+
Background: RGB = 255, 215, 175
Interstitial Fluid: RGB = 178, 220, 255
Cell interior: RGB = 169, 207, 161
Cell membrane: from left -> 5 down.
Cell membrane fill: 5 less than WHITE.
CA II fill: 3 less than WHITE.
Other Transporter fill: from right -> 2 up, 3 over
CO2 Icon fill: RGB = 203, 125, 164
Cl-

8. 9:00 Cellular ionic homeostasis/channel-transporter physiology
9:00 Cellular ionic homeostasis/channel-transporter physiology. George R. Dubyak, Case Western Res. Univ.
Lodish et al. (2000) Molecular Cell Biology
4th Edition [W.H. Freeman & Co.]

9. 10:00 Cellular volume homeostasis. Kevin Strange, Vanderbilt Univ.
Cell volume is regulated by the gain and loss of osmotically active solutes
normal
volume
Regulatory Volume
Increase (RVI)
Decrease (RVD)
solute gain
solute loss

10. 10:50 Cellular pH homeostasis. Walter F. Boron, Yale Univ.
Systemic pH regulation

11. 10:50 Cellular pH homeostasis. Walter F. Boron, Yale Univ.
Regulation: Acid extruders & loaders H+
OH–
Na+
Cl–
HCO3 – 2
V-type H+ pump
Na-H Exchanger
Na-Driven Cl-HCO3
Exchanger
Na/HCO3 Cotransporter
(1:2 stoichiometry) 3
(1:3 stoichiometry)
Cl-HCO3 Exchanger
Acid Extruders
Acid Loaders
pHi
Metabolism
Cellular pH regulation

12. Agenda – Cellular Homeostasis
8:00 – 8:10 In the beginning… there was the cell. M.F. Romero, Case Western Res. Univ.
8:10 – 9:00 Generation of membrane potential. S. Wright, Univ. of Arizona Col. of Med.
9:00 – 9:50 Cellular ionic homeostasis / channel-transporter physiology. G.R. Dubyak, Case Western Res. Univ.
9:50 – 10:00 Break / Coffee/ Tea
10:00 – 10:50 Cellular volume homeostasis. K. Strange, Vanderbilt Univ.
10:50 – 11:40 Cellular pH homeostasis. W.F. Boron, Yale Univ.
11:40 – 12:00 Final Discussion - All participants