GABAergic signaling in the rat pineal gland

YU, HAIJIE; BENITEZ, SERGIO; JUNG, SEUNG-RYOUNG ; KRUSE, MARTIN; SEO, JONG BAE; KOH, DUK-SU; MUÑOZ, ESTELA; HILLE, BERTIL

JOURNAL OF PINEAL RESEARCH

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0742-3098

Notar la primera coautoría compartida entre Yu y Benitez.Pinealocytes secrete melatonin at night in response tonorepinephrine released from sympathetic nerve terminals in the pineal gland.The gland also contains many other neurotransmitters whose cellulardisposition, activity, and relevance to pineal function are not understood.Here, we clarify sources and demonstrate cellular actions of theneurotransmitter c-aminobutyric acid (GABA) using Western blotting andimmunohistochemistry of the gland and electrical recording from pinealocytes.GABAergic cells and nerve fibers, defined as containing GABA and thesynthetic GAD67, were identified. The cells represent a subset of interstitialcells while the nerve fibers were distinct from the sympathetic innervation. TheGABAA receptor subunit a1 was visualized in close proximity of bothGABAergic and sympathetic nerve fibers as well as fine extensions amongpinealocytes and blood vessels. The GABAB1 receptor subunit was localized inthe interstitial compartment but not in pinealocytes. Electrophysiology ofisolated pinealocytes revealed that GABA and muscimol elicit strong inwardchloride currents sensitive to bicuculline and picrotoxin, clear evidence forfunctional GABAA receptors on the surface membrane. Applications ofelevated potassium solution or the neurotransmitter acetylcholine depolarizedthe pinealocyte membrane potential enough to open voltage-gated Ca2+channels leading to intracellular calcium elevations. GABA repolarized themembrane and shut off such calcium rises. In 48?72-h cultured intact glands,GABA application neither triggered melatonin secretion by itself nor affectednorepinephrine-induced secretion. Thus, strong elements of GABA signalingare present in pineal glands that make large electrical responses inpinealocytes, but physiological roles need to be found.