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J Neurophysiol 61: 1036-1052, 1989;
0022-3077/89 $5.00
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Journal of Neurophysiology, Vol 61, Issue 5 1036-1052, Copyright © 1989 by APS


ARTICLES

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

S. D. Erulkar and D. M. Wetzel
Department of Pharmacology, University of Pennsylvania Medical School, Philadelphia 19104.

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.





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