Chemical stimulation of Na transport through amiloride-blockable channels of frog skin epithelium.

The stimulation of apical Na permeability caused by a number of reagents effective from the outer side of the membrane was investigated by fluctuation analysis. In the epidermis of R. ridibunda, parachloromercuriphenyl sulfonate (PCMPS) and benzimidazolyl guanidine (BIG) increase the number (N0) of conducting Na channels by releasing channels from Na self-inhibition. As a consequence, the apparent macroscopic affinity for amiloride is increased. 5-dimethyl amiloride and trinitrobenzene sulfonate (TNBS) also cause reversible stimulation by increasing N0; here release from self-inhibition is less clear. With each of the four stimulators investigated, the Na channel current remained unaffected or was only marginally increased. In addition to its stimulatory effect, TNBS caused irreversible blockage of Na channels. Apart from their stimulatory effects, BIG and 5-dimethyl amiloride, both of which have a side-chain terminated with an amidino group, are high rate-blocking competitors of amiloride.