Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels

• Published in: Neurochemistry international Vol. 32; no. 2; pp. 153 - 162
• Main Authors: HAGBERG, G.-B, BLOMSTRAND, F, NILSSON, M, TAMIR, H, HANSSON, E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.02.1998
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Astrocytes - physiology; Biological and medical sciences; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - physiology; Calcium-Transporting ATPases - antagonists & inhibitors; Cells, Cultured; Cerebral Cortex - cytology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Heparin - pharmacology; Ion Channel Gating - drug effects; Isolated neuron and nerve. Neuroglia; Ketanserin - pharmacology; Rats; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Thapsigargin - pharmacology; Vertebrates: nervous system and sense organs; Cerebral cortex; Calcium; Rat; Neuroglia; Rodentia; Central nervous system; Ionic channel; Astrocyte; In vitro; 5-HT2 Serotonine receptor; Vertebrata; Mammalia; Brain (vertebrata)
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(97)00087-9

Mechanisms underlying the 5-HT2A receptor induction of intracellular Ca2+ mobilization and Ca2+ influx in type I astroglial cells in primary culture from newborn rat cerebral cortex were evaluated. The 5-HT-evoked Ca(2+)-transients, inhibited by the 5-HT2A antagonists ketanserin or 4-(4-fluorobenzoyl)-1-(4-phenylbutyl) piperidine oxalate, consisted of an initial peak caused by inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from internal stores, and a second sustained part which was due to Ca2+ transport over the plasma membrane. The responses were pertussis toxin-insensitive, suppressed by the phospholipase C inhibitor neomycin and were inhibited by the Ca(2+)-ATPase inhibitor thapsigargin. Furthermore, the responses were inhibited by the IP3 receptor antagonist heparin. When the second sustained part of the 5-HT-evoked response was studied, it was concluded that Ca2+ influx was not a result of opening of voltage operated calcium channels of either L, N or T-type. Instead it appeared that Ca2+ entered the cells through specialized voltage independent Ca2+ channels which were dependent of the IP3 production and subsequent Ca2+ release from internal stores. From this, we conclude that 5-HT opens Ca2+ channels in astrocytes which closely resemble depletion-operated Ca2+ channels (DOCCs).