Norepinephrine acts via α 2 adrenergic receptors to suppress N-type calcium channels in dissociated rat median preoptic nucleus neurons

Abstract

The median preoptic (MnPO) nucleus, a key CNS site for hydromineral and cardiovascular homeostasis, receives a dense norepinephrine innervation from brainstem autonomic centers. Since norepinephrine is known to influence neuronal excitability by modulating calcium channel function, we applied whole cell patch clamp techniques to study calcium currents in 116 dissociated MnPO neurons, including 30 cells identified by a retrograde label as projecting to the hypothalamic paraventricular nucleus. Norepinephrine (3–50 μM) suppressed high-voltage-activated calcium currents (HVA I Ca) in 80% of cells, selectively blockable by yohimbine and mimicked by UK14,304 and clonidine. The norepinephrine effect was relieved by strong prior depolarization, indicating a voltage-dependent component. Intracellular GTP-γ-S blocked the effect. Blockade by extracellular NEM suggested involvement of pertussis-toxin sensitive G-proteins. Based on pharmacological properties, these HVA I Cas had the following composition: 40–45% N-type (blockable by ω-conotoxin GVIA); 20–25% L-type (blockable by nimodipine); 15–20% P/Q-type (blockable by ω-agatoxin IVA). Since ∼75% of the norepinephrine effect was blockable with ω-conotoxin GVIA, we conclude that postsynaptic α 2 adrenoceptors preferentially suppress N-type calcium channels, revealing a novel mechanism whereby norepinephrine can modulate excitability in MnPO neurons.