Effects of testosterone on synaptic efficacy at neuromuscular junctions in a sexually dimorphic muscle of male frogs.

Abstract

1. The effects of testosterone on synaptic efficacy were studied in the flexor carpi radialis, a sexually dimorphic forelimb muscle involved in frog clasping behaviour. Male Xenopus laevis frogs were castrated and then given either testosterone-filled implants (CT frogs) or empty implants (C frogs) for 2, 8 or 16 weeks. 2. Intracellular recordings were made from fibres in the shoulder region and in a region midway between the elbow and wrist. These regions are mainly innervated by spinal nerve 2 (SN2) and spinal nerve 3 (SN3), respectively. 3. In CT muscles, the percentage of fibres that failed to generate an action potential in response to a single nerve stimulus was greater than in C muscles. The percentage of such fibres was greater among SN2 fibres than among SN3 fibres. 4. The input resistance and membrane time constant were lower in CT muscles than in C muscles for SN2 fibres but not for SN3 fibres. The action potential threshold was lower in CT muscles than in C muscles. In SN2 fibres, the action potential threshold was higher than in SN3 fibres. 5. Quantal content with 1 Hz nerve stimulation and miniature endplate potential (MEPP) frequency did not differ between CT and C junctions. However, both parameters were lower at SN2 junctions than at SN3 junctions. The amplitude of MEPPs was lower in CT muscles than in C muscles only for SN2 junctions. 6. Facilitation of transmitter release with 70 or 10 Hz nerve stimulation was greater at CT junctions than at C junctions. Also, SN2 junctions showed greater facilitation than SN3 junctions. 7. We hypothesize that the more androgen-sensitive SN2 junctions, which have lower quantal content and greater facilitation, belong to motor units that are tonically active, fatigue resistant, and contract more slowly. The less androgen-sensitive SN3 junctions, which have higher quantal content and less facilitation, may belong to motor units that are phasically active, fatigable and contract more rapidly. Testosterone enhances these differences such that flexor carpi radialis junctions are better adapted to the functional demands of clasping.

Enhanced muscle fatigue occurs in male but not female ASIC3−/− mice

“…Furthermore, testosterone increases intracellular calcium in myocytes producing increases in phosphorylation and transcription factors through a G proteinlinked receptor (16). In agreement, testosterone administration to myocytes decreases the action potential threshold and increases synaptic facilitation resulting in an enhancement of synaptic efficiency in the flexor carpi radialis muscle of the frog (43). Thus, testosterone can have relatively fast effects on the function of the myocyte that would affect the efficacy of synaptic transmission through phosphorylation of ion channels.…”

“…In contrast, several studies show an increase in muscle strength following testosterone replacement therapy in men with low levels of testosterone (5,6,18), and testosterone enhances force and resistance to fatigue in normal males (2,65). In parallel, androgen receptors are located on muscle fibers (1,42) and long-term treatment of orchidectomized male mice with testosterone alters the neuromuscular junction to enhance synaptic efficacy (43). The effect of fatigue after testosterone treatment is muscle type-specific being observed in the soleus muscle Type I fibers but not in the extensor digitorum longus muscle Type II fibers (2).…”

Facilitation at the sexually differentiated laryngeal synapse of Xenopus laevis

“…In mouse diaphragm, facilitation was examined over a range of quantal contents similar to that used in this study (0.1-3.0); again, no correlation between strength and facilitation was found (Bain and Quastel 1992). A variation in facilitation without a variation in strength has been demonstrated in another androgensensitive muscle of X. laevis: in the flexor carpi radialis, testosterone enhances facilitation without affecting release to a single stimulus (Nagaya and Herrera 1995). Mallart and Martin's (1968) study of frog sartorius showed that there was some dependence of facilitation on quantal content but only for the weakest synapses.…”

Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists

“…Subsequently, a greater force was produced and testosterone concentration was elevated. Additionally, an acute increase in testosterone can directly influence force production by facilitating neurotransmitter release (Nagaya and Herrera 1995). Thus, the ingestion of caffeine, together with acute elevations in plasma testosterone may act synergistically on the CNS to directly increase force production and improve performance.…”