Monovalent Cation Homeostasis

ATPases: P-type, V-type, F-type

interconvert chemical energy (ATP) and ion gradient energy (concentration/electrochemical gradient across membrane)

V and F transport only protons

P and V only hydrolyze ATP

F can also produce ATP by running in reverse (high ADP and low H⁺ in mitochondrial matrix)

all are driven by ATP/ADP ratio

The Na-K ATPase

Moves Na⁺Out and K⁺In

after this, membrane is more permeable to K⁺, so some K⁺moves out

K⁺exit produces more positive charge outside

There is already more Na⁺outside, so this charge difference means Na⁺really wants to come in

The cell uses this dual Na⁺gradient (concentration/electrostatic) for many biological processes.

So the Na-K ATPase is very important (it uses one third of all cell energy)

Peculiar Features of this Protein:

3 Na⁺out per 2 K⁺in, so it is electrogenic (although this current does NOT directly produce membrane potential—see above)
found in plasma membrane of all cells (especially neurons)
always saturated with ATP under cellular conditions
2 subunits—alpha binds Na⁺, K⁺, ATP, ouabain, etc.; beta is glycosylated and controls localization and ATPase activity
it is called a P-type ATPase because it is phosphorylated at an aspartate residue
the high energy Asp-PO4 ester linkage is used to drive the reaction
Na⁺ stimulates kinase, and K⁺ stimulates phosphatase, so there are 2 steps:

(1) dephosphorylated enzyme releases 2 K⁺ inside and binds 3 Na⁺; this stimulates the kinase.
(2) phosphorylated enzyme releases 3 Na⁺ outside and binds 2 K⁺; this stimulates the phosphatase. Go to 1.

Digitalis (ouabain)

glycosidic steroid—acts only on Na-K ATPase

competes with K⁺, so it turns off the phosphatase and inhibits the enzyme

Na⁺ inside the cell increases, removing the concentration/electrostatic Na⁺ gradient

Na⁺/Ca⁺⁺ antiport depends on this gradient, so it pushes out less Ca⁺⁺

more Ca⁺⁺ in the cell causes stronger beats

Only 10% of the Na-K ATPase channels should be inhibited, since inhibiting more would be lethal (cell volume, pH, and membrane potential are controlled by the Na-K ATPase)

Also, dosage must be controlled for intracellular K⁺ concentration (need more if hyperkalemic)