Thallium interaction with the gastric (K, H)-ATPase

Area of Science:

• Biochemistry
• Membrane Transport
• Enzyme Kinetics

Background:

• The gastric (K, H)-ATPase is crucial for acid secretion, catalyzing electroneutral H+ for K+ exchange.
• Understanding cation interactions with this enzyme is vital for elucidating its transport mechanism.

Purpose of the Study:

• To investigate the role of thallium ions (Tl+) as a substitute for potassium (K+) in gastric (K, H)-ATPase activity.
• To characterize the transport and permeability properties of Tl+ across gastric vesicle membranes.

Main Methods:

• Enzyme kinetic assays measuring hydrolytic activity of gastric (K, H)-ATPase.
• pH gradient measurements in gastric vesicles to assess transport.
• Thallium ion (Tl+) efflux and influx studies using gastric vesicles and liposomes.
• Permeability measurements comparing Tl+ and rubidium chloride (RbCl).

Main Results:

• Tl+ effectively substitutes for K+ in hydrolyzing ATP, with a higher affinity (Kd = 90 µM) than K+ (Kd = 870 µM).
• Tl+ supports ATP-dependent pH gradient formation and Tl+ efflux from gastric vesicles.
• High external Tl+ concentrations (>3.0 mM) inhibit ATPase hydrolysis and pH gradient formation, attributed to Tl+ binding at an external site.
• Gastric vesicles and liposomes exhibit high permeability to Tl+ (t1/2 ≈ 1.0 min), significantly higher than RbCl (t1/2 = 46 min).
• Excessive Tl+ concentrations dissipate proton gradients, indicating uncoupling of H+ transport.

Conclusions:

• Tl+ activates gastric (K, H)-ATPase, acting as a K+ mimic.
• The high permeability of Tl+ across lipid bilayers leads to uncoupling of proton transport at elevated concentrations.
• This uncoupling effect limits Tl+'s utility as a probe for studying gastric H+ transport mechanisms.