5 alpha-dihydrotestosterone has nonspecific effects on membrane channels and possible genomic effects on ACh-activated channels.

1. Myotubes cultured from adult male Xenopus laevis laryngeal muscle have been found to express androgen receptors. 2. Using patch-clamp techniques, it was found that 5 alpha-dihydrotestosterone (5 alpha-DHT) can act directly at membranes of these myotubes to alter the kinetic properties of acetylcholine- (ACh) activated single channels. 3. When the culture medium contains 5 alpha-DHT for greater than 6 days, the androgen acts through its receptors to markedly increase ACh-activated, single-channel conductances and alter single-channel kinetics. These effects do not occur if the antiandrogen, flutamide, which prevents the androgen from combining with its receptor, is added to the medium before the addition of the 5 alpha-DHT. These effects also do not occur in myotubes cultured from quadriceps femoris muscles that have much lower levels of specific androgen receptor. 4. When alpha-bungarotoxin (alpha-BTX) is added to the medium for 3 h before recording, no ACh channels can be recorded from myotubes in control medium within 5 h after washout of the alpha-BTX. However, when the culture medium contains 5 alpha-DHT for greater than or equal to 6 days, ACh channels can be recorded within 8 min of the washout of the alpha-BTX. 5. The results suggest that 5 alpha-DHT may act to alter the properties of ACh-activated ion channels at multiple sites in excitable cells.