Testosterone modulates Cav2.2 calcium channels´ functional expression at rat levator ani neuromuscular junction

NUDLER SI; PAGANI MR; URBANO FJ; MCENERY MW; UCHITEL OD

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: New York, USA.; Año: 2005 vol. 134 p. 817 - 826

0306-4522

Spinal nucleus of bulbocavernosus and its target musculature, the bulbocavernosus and levator ani muscles, are sexually dimorphic, and their sexual differentiation depends on plasmatic levels of testosterone. Electrophysiological and immunocytochemical studies have demonstrated that at mammalian adult neuromuscular junctions only P/Qtype Ca-channels (Cav2.1), mediate evoked transmitter release. Here we report that N-type Ca channel (Cav2.2) blocker omega-Conotoxin GVIA, as well as Cav2.1 blocker omega-Agatoxin IVA, significantly reduced quantal content of transmitter release by  80% and 70% respectively at levator ani muscle of the adult rats, indicating that neuromuscular transmission is jointly mediated by both types of channels. In these synapses, we also observed that castration and restitution of plasmatic testosterone in rats resulted in changes in the sensitivity to omega-Conotoxin GVIA. Castration induced, whereas testosterone treatment avoided, functional loss of Cav2.2, as mediators of transmitter release in these synapses. Strikingly, the expression and localization of alpha-1B subunits, which form the pore of the Cav2.2 channel, were similar at control, gonadectomized and gonadectomized testosterone-treated rats, suggesting that testosterone may regulate the coupling mechanisms between Cav2.2 and transmitter release at the neuromuscular junctions of these sexually dimorphic motoneurons.