Voltage‐Dependent Calcium Channels in Ventromedial Hypothalamic Neurones of Postnatal Rats: Modulation by Oestradiol and Phenylephrine

Abstract

Oestradiol actions in the hypothalamus play an important role in reproductive behaviour. Oestradiol treatment in vivo induces alpha(1b)-adrenoceptor mRNA and increases the density of alpha(1B)-adrenoceptor binding in the hypothalamus. Oestradiol is also known to modulate neuronal excitability, in some cases by modulating calcium channels. We assessed the effects of phenylephrine, an alpha(1)-adrenergic agonist, on low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium channels in ventromedial hypothalamic (VMN) neurones from vehicle- and oestradiol-treated female rats. Whole-cell and gramicidin perforated-patch recordings were obtained, with barium as the charge carrier. In the absence of phenylephrine, oestradiol treatment increased the magnitude of LVA currents compared to controls, but had no effect on HVA currents. Phenylephrine enhanced HVA currents in a significantly greater proportion of neurones from oestradiol-treated rats (76%) than from vehicle-treated (41%) rats. The L-channel blocker nifedipine abolished this oestradiol effect on phenylephrine-enhanced HVA currents. Preincubating slices with the N-type channel blocker omega-conotoxin GVIA completely blocked the phenylephrine response, suggesting that the N-type channel is essential. Phenylephrine also stimulated LVA currents in approximately two-thirds of neurones in slices from both vehicle- and oestradiol-treated rats. Our data show that oestradiol increases LVA currents in the VMN. Oestradiol also amplifies alpha(1)-adrenergic signalling by increasing the proportion of neurones showing phenylephrine-stimulated HVA currents mediated by N- and L-type calcium channels. In this way, oestradiol may increase excitatory responses to arousing adrenergic inputs to VMN neurones governing oestradiol-dependent reproductive behaviour.