RT Journal Article
SR Electronic
T1 Adrenergic calcium signaling in astrocyte networks within the hippocampal slice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5535
OP 5550
DO 10.1523/JNEUROSCI.15-08-05535.1995
VO 15
IS 8
A1 Duffy, S
A1 MacVicar, BA
YR 1995
UL http://www.jneurosci.org/content/15/8/5535.abstract
AB Norepinephrine (NE) and glutamate (Glu) initiate intracellular calcium ([Ca2+]i) transients, oscillations, and intracellular [Ca2+]i waves in cultured astrocytes. To further elucidate the significance of NE- and Glu-evoked astrocytic [Ca2+]i signaling to neuron-astrocyte communication in the mature CNS, [Ca2+]i of astrocyte networks within hippocampal slices (P21–42) was measured during bath application of NE and Glu receptor agonists. Astrocytes in stratum radiatum were identified by highly negative membrane potentials (75 +/- 3 mV), absence of action potentials, and dye coupling following intracellular injection of the [Ca2+]-sensitive dye calcium orange. NE (2–100 microM) evoked [Ca2+]i increases (7 of 8 slices, 24 of 24 cells in responding slices) characterized by an initial rise, 20–50 sec to peak, followed by a slower return to baseline (over approximately 8 min). The alpha 1- agonist phenylephrine (PE) (10–100 microM) evoked complex [Ca2+]i signals (22 of 26 slices, 90 of 90 cells in responding slices) composed of both a prolonged component (5.1 +/- 1.8 min), synchronized in neighboring cells, and multiple, mainly asynchronous [Ca2+]i spikes (25.0 +/- 11.6 sec). PE responses were completely blocked by the alpha 1-antagonist prazosin (200 nM, n = 4 slices), but not by the alpha 2- antagonist yohimbine (n = 3 slices). The alpha 2-agonist clonidine (10- 100 microM) did not increase [Ca2+]i (n = 4 slices). alpha 1-mediated [Ca2+]i transients were observed after removal of extracellular [Ca2+]o (n = 8 of 9 slices), indicating PE-induced Ca2+ release from intracellular stores. Adrenergic responses were mediated by alpha 1- receptors localized to astrocytes because PE and NE increased [Ca2+]i of acutely isolated hippocampal astrocytes. Glu (0.75–2.0 mM) did not increase astrocytic [Ca2+]i in slices (0 of 7), even in the presence of the Glu uptake inhibitor L-trans-pyrrollidine-2,4-dicarboxylic acid (PDC) (0 of 5 slices), or in acutely isolated astrocytes (0 of 7 cells). The metabotropic agonist t-ACPD (30 or 50 microM) did not increase astrocytic [Ca2+]i in hippocampal slices (0 of 5), while kainate (200 microM or 1 mM) induced brief (1–2 min) [Ca2+]i increases only rarely (2 of 8 applications in 6 slices). These results support a primary role of NE release and alpha 1-adrenoceptor stimulation in neuron-astrocyte communication in the mature CNS.