Lecture 6: Regulation of Intracellular Ion Concentrations

What does the Na-K pump maintain?

low intracellular Na, high intracellular K

What does the Ca-H pump maintain?

low intracellular Ca compared to extracellular Ca

What does the Na-Ca exchanger maintain?

low intracellular Ca compared to extracellular Ca

Why is chloride concentration modestly above equilibrium in most cells?

Cl- uptake via the Cl-HCO3 exchanger and Na/K/Cl cotransporter balances the passive Cl- efflux through channels

What keeps the intracellular pH and HCO3 concentration about their equilibrium values?

• Na-H exchanger

• Na+-driven Cl-HCO3

What is the primary mediator of Na+ extrusion and K+ accumulation?

the Na/K pump

What helps to establish the inside-negative V_m?

electrogenicity

Which toxin inhibits the Na/K pump?

ouabain

What is ouabain?

a plant-derived toxin; used to poison arrows for hunting

How does ouabain inhibit the Na/K pump?

the toxin has a high affinity for the extracellular side and will block the pore—stopping pump function

What, specifically, does ouabain bind to the Na/K pump?

the E₂-P

What does active K+ accumulation by the Na/K pump create?

outward K+ concentration gradient

Describe K+ channels.

• exit of K+ via these channels

• main driver of inside-negative V_m

• down electrochemical gradient

What would happen to V_m if K+ channels were blocked?

• V_m increases and becomes less negative

• larger K+ concentration

For what purposes do cells harness the energy of Na+ energy for?

• epithelial cells: express Na+ channel (ENaC) on one side of the cell (apical) and Na-K pump on other side (basolateral) → transepithelial transport

• excitable cells: voltage-dependent Na+ channels drive action potential generation with Na+ entry

• all cells: to drive secondary active transport (cotransporters and exchangers)

Which ion has the largest electrochemical gradient?

Ca²⁺

What are Ca²⁺ channels gated by?

voltage or ligands

True or False: Rapid entry of Ca²⁺ into cells occurs in short bursts and is instantaneous.

true

How is intracellular Ca²⁺ kept so low?

SERCA

What does SERCA stand for?

sarcoplasmic and endoplasmic reticulum calcium ATPase

What does SERCA exchange?

exchanges 2 Ca²⁺ and 2 H⁺ per ATP hydrolyzed

What does SERCA do?

sequesters cytosolic Ca²⁺ in intracellular stores

True or False: Ca²⁺ can be released into the cytoplasm as part of a signal transduction (via IPTR).

true

What allows the release of Ca²⁺ into the cytosol?

IP₃

What does PMCA stand for?

plasma membrane calcium ATPase

What does PMCA exchange?

1 Ca²⁺ and 1 H⁺ per ATP hydrolyzed

What does PMCA do?

extrudes Ca²⁺ from the cell

List the steps in how calcium regulates PMCA.

1. as intracellular calcium increases, calcium binds to calmodulin

2. calcium-CaM binds to PMCA

3. reveals catalytic domain, lowers threshold of calcium needed for pump to start extruding calcium

4. as intracellular calcium decreases, calcium-CaM levels fall

5. calcium-CaM disassociates from the pump

6. pump returns to inactive state

What is the NCX?

a Na-Ca exchanger

What does NCX play a key role in?

extruding Ca²⁺ when intracellular calcium concentration rises substantially above normal levels

What does NCX help to restore?

restores lower intracellular calcium concentration levels when large influxes of Ca²⁺ occur

True or False: Na-Ca exchanger and Ca²⁺ pump in the plasma membrane both extrude Ca²⁺ from the cell.

true

What uptakes intracellular chloride?

• Cl-HCO₃ exchanger

• NKCC

What extrudes intracellular chloride?

KCC

True or False: There is passive loss or entry of Cl^- through anion-selective channels (depending on V_m and E_Cl.

true

What is acid extrusion?

transport of acid out of cell or base into cell

When are acid extruders stimulated and inhibited?

• stimulated when the cell is acidified

• inhibited when the cell is alkalinized

List the acid extruders.

• Na-H exchanger

• Na+-driven Cl-HCO₃ exchanger

• Na/HCO₃ cotransporters

True or False: 1:1 and 1:2 stoichiometries move HCO₃^- into the cell.

true

True or False: Acid loaders reflect a loss of base from the cell.

true

List the acid loaders.

• Cl-HCO₃ exchanger

• Na/HCO₃ cotransporter

True or False: 1:3 stoichiometry moves HCO₃^- out of the cell.

true