Activation of alpha-1 adrenergic receptors increases cytosolic calcium in neurones of the paraventricular nucleus of the hypothalamus.

Norepinephrine (NE) activates adrenergic receptors (ARs) in the hypothalamic paraventricular nucleus (PVN) to increase excitatory currents, depolarise neurones and, ultimately, augment neuro-sympathetic and endocrine output. Such cellular events are known to potentiate intracellular calcium ([Ca ] ); however, the role of NE with respect to modulating [Ca ] in PVN neurones and the mechanisms by which this may occur remain unclear. We evaluated the effects of NE on [Ca ] of acutely isolated PVN neurones using Fura-2 imaging. NE induced a slow increase in [Ca ] compared to artificial cerebrospinal fluid vehicle. NE-induced Ca elevations were mimicked by the α -AR agonist phenylephrine (PE) but not by α -AR agonist clonidine (CLON). NE and PE but not CLON also increased the overall number of neurones that increase [Ca ] (ie, responders). Elimination of extracellular Ca or intracellular endoplasmic reticulum Ca stores abolished the increase in [Ca ] and reduced responders. Blockade of voltage-dependent Ca channels abolished the α -AR induced increase in [Ca ] and number of responders, as did inhibition of phospholipase C inhibitor, protein kinase C and inositol triphosphate receptors. Spontaneous phasic Ca events, however, were not altered by NE, PE or CLON. Repeated K -induced membrane depolarisation produced repetitive [Ca ] elevations. NE and PE increased baseline Ca , whereas NE decreased the peak amplitude. CLON also decreased peak amplitude but did not affect baseline [Ca ] . Taken together, these data suggest receptor-specific influence of α and α receptors on the various modes of calcium entry in PVN neurones. They further suggest Ca increase via α -ARs is co-dependent on extracellular Ca influx and intracellular Ca release, possibly via a phospholipase C inhibitor-mediated signalling cascade.