Amphotericin B and K+ transport across excised toad urinary bladder

Area of Science:

• Physiology
• Pharmacology
• Membrane Biology

Background:

• The antifungal drug amphotericin is known to alter cell membrane permeability.
• Understanding its specific effects on epithelial tissues like the bladder is crucial for therapeutic applications and safety.

Purpose of the Study:

• To investigate the effects of amphotericin on the electrical properties and ion transport of the bladder.
• To elucidate the mechanisms by which amphotericin influences ion permeability, particularly for potassium and sodium.

Main Methods:

• Measurement of transmural electric potential difference (PD) and conductance in isolated bladders.
• Analysis of unidirectional fluxes of radiolabeled ions (Na+, K+, SO42-) across the short-circuited bladder.
• Manipulation of ion concentrations in bathing solutions and assessment of drug effects with and without ouabain pretreatment.

Main Results:

• Amphotericin increased bladder conductance and altered potential difference in the presence of a potassium gradient.
• The drug significantly increased unidirectional fluxes of Na+ and K+, but not SO42-.
• A marked asymmetry in K+ flux (mucosal-to-serosal vs. serosal-to-mucosal) was observed, suggesting a selective pathway, which was influenced by K+ concentration and ouabain.

Conclusions:

• Amphotericin appears to induce a paracellular, potassium-selective pathway in the bladder.
• The drug also facilitates Na+ isotope exchange and K+ secretion, though K+ secretion is not tightly coupled to Na+ transport.
• These findings provide insights into the membrane transport mechanisms affected by amphotericin in epithelial tissues.