Phenamil: An irreversible inhibitor of sodium channels in the toad urinary bladder
- Cite this article as:
- Garvin, J.L., Simon, S.A., Cragoe, E.J. et al. J. Membrain Biol. (1985) 87: 45. doi:10.1007/BF01870698
- 78 Downloads
Several new amiloride analogues and two reported photoaffinity analogues were tested for irreversible inhibition of short-circuit current,Isc, in toad bladder. Bromoamiloride, a photoaffinity analogue, induced 40% irreversible inhibition at 500 μm after irradiation with ultraviolet light ≥320 nm. Iodoamiloride caused no irreversible inhibition. Of the new analogues tested, only 3,5-diamino-6-chloro-N-[(phenylamino) aminomethylene] pyrazinecarboxamide,phenamil, irreversibly inhibitedIsc at concentrations of 0.05 to 5 μm when added to the mucosal solution. Irreversible inhibition ofIsc by phenamil may be attributed to specific blockage of the mucosal sodium channels, which depended on: 1) time of exposure; 2) mucosal pH: 3) mucosal sodium concentration. For example, 5 μm phenamil irreversibly inhibitedIsc by 38% in 103mm Na at pH 8.6 and nearly 75% in 30mm Na at pH 6.4 after a 40-min exposure. Irreversible inhibition occurred in two phases with time constants of ≤10 min and approximately 140 min. Due to its irreversible nature, phenamil may be used to measure channel density.