Hippocampal Astrocytes Exhibit Ca2+ ‐Elevating Muscarinic Cholinergic and Histaminergic Receptors In Situ

Abstract: Recent findings suggest that astrocytes respond to neuronally released neurotransmitters with Ca 2+ elevations. These Ca 2+ elevations may trigger astrocytes to release glutamate, affecting neuronal activity. Neuronal activity is also affected by modulatory neurotransmitters that stimulate G protein‐coupled receptors. These neurotransmitters, including acetylcholine and histamine, might affect neuronal activity by triggering Ca 2+ ‐dependent release of neurotransmitters from astrocytes. However, there is no physiological evidence for histaminergic or cholinergic receptors on astrocytes in situ. We asked whether astrocytes have these receptors by imaging Ca 2+ ‐sensitive dyes sequestered by astrocytes in hippocampal slices. Our results show that immunocytochemically identified astrocytes respond to carbachol and histamine with increases in intracellular free Ca 2+ concentration. The H1 histamine receptor antagonist chlorpheniramine inhibited responses to histamine. Similarly, atropine and the M1‐selective muscarinic receptor antagonist pirenzepine inhibited carbachol‐elicited responses. Astrocyte responses to histamine and carbachol were compared with responses elicited by α 1 ‐adrenergic and metabotropic glutamate receptor agonists. Individual astrocytes responded to different subsets of receptor agonists. Ca 2+ oscillations were the prevalent response pattern only with metabotropic glutamate receptor stimulation. Finally, functional α 1 ‐adrenergic receptors and muscarinic receptors were not detected before postnatal day 8. Our data show that astrocytes have acetylcholine and histamine receptors coupled to Ca 2+ . Given that Ca 2+ elevations in astrocytes trigger neurotransmitter release, it is possible that these astrocyte receptors modulate neuronal activity.