Calcium Signalling in Mouse Bergmann Glial Cells Mediated by α₁‐adrenoreceptors and H₁ Histamine ‐ Receptors

Abstract

The presence of adrenergic and histaminergic receptors in Bergmann glial cells from cerebellar slices from mice aged 20-25 days was determined using fura-2 Ca2+ microfluorimetry. To measure the cytoplasmic concentration of Ca2+ ([Ca2+]i), either individual cells were loaded with the Ca2+-sensitive probe fura-2 using the whole-cell patch-clamp technique or slices were incubated with a membrane permeable form of the dye (fura-2/AM) and the microfluorimetric system was focused on individual cells. The monoamines adrenalin and noradrenalin (0.1-10 microM) and histamine (10-100 microM) triggered a transient increase in [Ca2+]i. The involvement of the alpha1-adrenoreceptor was inferred from the observations that monoamine-triggered [Ca2+]i responses were locked by the selective alpha1-adreno-antagonist prazosin and were mimicked by the alpha1-adreno-agonist phenylephrine. The monoamine-induced [Ca2+]i signals were not affected by beta- and alpha2-adrenoreceptor antagonists (propranolol and yohimbine), and were not mimicked by beta- and alpha2-adrenoreceptor agonists (isoproterenol and clonidine). Histamine-induced [Ca2+]i responses demonstrated specific sensitivity to only H1 histamine receptor modulators. [Ca2+]i responses to monoamines and histamine did not require the presence of extracellular Ca2+ and they were blocked by preincubation of slices with thapsigargin (500 nM), indicating that the [Ca2+]i responses were recorded after application of aspartate, bradykinin, dopamine, GABA, glycine, oxytocin, serotonin, somatostatin, substance P, taurine or vasopressin. We conclude that cerebellar Bergmann glial cells are endowed with alpha1-adrenoreceptors and H1 histamine receptors which induce the generation of intracellular [Ca2+]i signals via activation of Ca2+ release from inositol-1,4,5-trisphosphate-sensitive intracellular stores.

Recent advances in (patho)physiology of astroglia

“…Often the receptor patterns expressed by astroglia match the receptors present in their immediate neuronal neighbourhood. For example Bergman glial cells and their intimate associates, Purkinje neurones, express receptors for adrenalin, histamine, glutamate, GABA and adenosine 5'-triphosphate (ATP), these receptors being congruent to the neurotransmitters released in this anatomical region [34][35][36] . The most widespread receptors in astroglia are represented by glutamate receptors and purinoceptors.…”

Patching the glia reveals the functional organisation of the brain

“…These cells express receptors for noradrenalin, glutamate, GABA, histamine and ATP, i.e. the receptors activated by neurotransmitters released from terminals present in the Purkinje layer of cerebellum [43, 45,47,62,63]; the closest neighbour of the Bergmann glial cell, the Purkinje neurone, also expressed receptors for these neurotransmitters [44]. Subsequently, similar matching relations between neuronal and glial receptor expression was found in the spinal cord, where both astrocytes and neurones possess glycine receptors acting as a main neurotransmitter in this region [42,69].…”

Glutamatergic and Purinergic Receptor-Mediated Calcium Transients in Bergmann Glial Cells

“…This is exemplified by Bergmann glial cells (BGs) of the cerebellar cortex. Exogenous application of agonists such as histamine, noradrenaline, glutamate, or ATP (Kirischuk et al, 1995(Kirischuk et al, , 1996(Kirischuk et al, , 1999Beierlein and Regehr, 2006) induces intracellular Ca 2ϩ mobilization in BGs. [Ca 2ϩ ] i elevations in BGs have also been observed during synaptic activity.…”