Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Abstract

The hypothalamic paraventricular nucleus (PVN) neurons that project to the spinal intermediolateral cell column and brainstem are important for the control of sympathetic outflow. Stimulation of ␣ 1 adrenergic receptors in the PVN increases sympathetic outflow, but the cellular mechanisms remain unclear. In this study, we determined the role of ␣ 1 adrenergic receptors in the regulation of glutamatergic and GABAergic synaptic inputs to spinally projecting PVN neurons. Whole-cell and cell-attached patch-clamp recordings were performed on retrogradely labeled PVN-spinal neurons in rat brain slices. Bath application of 10 to 100 M phenylephrine, an ␣ 1 adrenergic receptor agonist, significantly increased the frequency of spontaneous excitatory postsynaptic currents in a concentration-dependent manner. This effect was blocked by the ␣ 1 adrenergic receptor antagonists prazosin or corynanthine. Phenylephrine also significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) but not the amplitude and decay constant of mEPSCs. Furthermore, activation of ␣ 1 adrenergic receptors with phenylephrine or cirazoline significantly decreased the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, and this effect also was blocked by corynanthine. In addition, 50 M phenylephrine significantly increased the firing rate of 13 labeled PVN neurons from 3.16 Ϯ 0.42 to 5.83 Ϯ 0.65 Hz. However, phenylephrine failed to increase the firing of most labeled PVN neurons in the presence of GABA A and ionotropic glutamate receptor antagonists. Thus, these data suggest that activation of ␣ 1 adrenergic receptors increases the excitability of PVN presympathetic neurons primarily through augmentation of glutamatergic tone and attenuation of GABAergic inputs.

Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus

“…Noradrenaline increases the frequency of IPSCs by activating the ␣ 1 -adrenoceptors on the soma, but decreases their frequency by activating the ␣ 2 -adrenoceptors (Chong et al 2004;Daftary et al 2000;Han et al 2002;Li et al 2005) and ␣ 1 -adrenoceptors on the terminal of GABAergic neurons (Chen et al 2006). These receptors were further identified as ␣ 1A/1L and ␣ 2A subtypes, respectively (Chong et al 2004).…”

Effects of Alpha 1- and Alpha 2-Adrenoreceptor Stimulation on Galanin mRNA Expression in Primary Cultured Superior Cervical Ganglion Neurons

“…Different subtypes of adrenoreceptors have different actions. Activation or inhibition of distinct adrenoreceptors infl uences tone of sympathetic nervous system or neurotransmitter synthesis or release (Chen et al, 2006). In the present study, the regulation of Gal mRNA expression in SCG neurons by activation of alpha 2-adrenoreceptors may be involved in the mechanism of sympathetic-sensory coupling even the mechanism is not fully understood.…”

“…Activation or inhibition of distinct adrenoreceptors may result in different effects (Chen et al, 2006). The dual pro-and anti-infl ammatory role of the sympathetic nervous system in infl ammatory conditions may relate to an intricate shift from beta-to-alpha adrenergic signaling (Straub and Harle, 2005).…”

Involvement of Hypothalamic Periventricular GABAergic Nerves in the Central Pressor Response to Clonidine in Freely-Moving Conscious Rats

“…These findings strongly suggest that GABAergic neurons and GABA A receptors in the PVN are responsible for the clonidineinduced pressor response. GABAergic neurons in the PVN have been shown to have presynaptic α 2 -adrenoceptors, which inhibit GABAergic activity in the PVN (10,12). Taken together, it seems likely that clonidine stimulates presynaptic α 2 -adrenoceptors in GABAergic neurons to attenuate GABAergic neurotransmission, probably reducing release of GABA, resulting in decreased inhibitory GABAergic activity to excitatory PVN neurons.…”