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

Norepinephrine ( NE ) activates adrenergic receptors ( AR s) 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 2+ ] i ); however, the role of NE with respect to modulating [Ca 2+ ] i in PVN neurones and the mechanisms by which this may occur remain unclear. We evaluated the effects of NE on [Ca 2+ ] i of acutely isolated PVN neurones using Fura‐2 imaging. NE induced a slow increase in [Ca 2+ ] i compared to artificial cerebrospinal fluid vehicle. NE ‐induced Ca 2+ elevations were mimicked by the α 1 ‐ AR agonist phenylephrine ( PE ) but not by α 2 ‐ AR agonist clonidine ( CLON ). NE and PE but not CLON also increased the overall number of neurones that increase [Ca 2+ ] i (ie, responders). Elimination of extracellular Ca 2+ or intracellular endoplasmic reticulum Ca 2+ stores abolished the increase in [Ca 2+ ] i and reduced responders. Blockade of voltage‐dependent Ca 2+ channels abolished the α 1 ‐ AR induced increase in [Ca 2+ ] i and number of responders, as did inhibition of phospholipase C inhibitor, protein kinase C and inositol triphosphate receptors. Spontaneous phasic Ca 2+ events, however, were not altered by NE , PE or CLON . Repeated K + ‐induced membrane depolarisation produced repetitive [Ca 2+ ] i elevations. NE and PE increased baseline Ca 2+ , whereas NE decreased the peak amplitude. CLON also decreased peak amplitude but did not affect baseline [Ca 2+ ] i . Taken together, these data suggest receptor‐specific influence of α 1 and α 2 receptors on the various modes of calcium entry in PVN neurones. They further suggest Ca 2+ increase via α 1 ‐ AR s is co‐dependent on extracellular Ca 2+ influx and intracellular Ca 2+ release, possibly via a phospholipase C inhibitor‐mediated signalling cascade.