α7 Nicotinic acetylcholine receptors induced an increase in intracellular calcium in supraoptic nucleus neurons (1126.20)

Abstract

The SON neurons synthesize oxytocin (OT) and vasopressin (VP) and receive cholinergic innervations. AchRs are expressed in SON. Activation of AchRs has been implicated in the control of water loss via VP release and also regulates release of OT, an anorexic agent. Deficits in OT are associated with human obesity. Thus, the brain cholinergic system may regulate food intake via modulation of OT neurons. Previous studies have demonstrated that activation of nAchRs stimulated a rise in [Ca++]i in SON neurons. In our current studies, live‐cell calcium imaging was used to determine the subtypes of nAchRs responsible. Mouse hypothalamic explants that include SON were loaded with the calcium sensitive dye, Fura‐2AM. Changes in [Ca++]i were monitored by changes in the 340/380 nm emission. Ach (5 mM) induced a [Ca++]i rise in the absence or presence of atropine (10 μM, muscarinic AchR antagonist) in wild type (WT) mice. In the presence of atropine, the amplitude of the [Ca++]i rise was reduced in WT mice while in α7 nAchR knockout (KO) mice, Ach only generated a small increase in [Ca++]i. Furthermore, in the additional presence of DHPE, an antagonist for α4β2 nAchRs, the rise in [Ca++]i in KO mice was completely absent. These experiments demonstrated that in SON neurons, both α7 and α4β2 nAchRs are functionally present and upon activation, generate calcium signals. Future studies will identify the OT vs VP phenotype of the responsive neurons.Grant Funding Source: Supported by a NORC pilot award from NIH DK048250.