Serotonin induces inward potassium and calcium currents in rat cortical astrocytes

Ca 2+ imaging and patch-clamp techniques were used to study the effects of serotonin (5-HT) on ionic conductances in rat cortical astrocytes. 1 and 10 μM serotonin caused a transient increase in intracellular calcium (Ca 1) levels in fura-2AM-loaded cultured astrocytes and in astrocytes acutely isolated and then cultured in horse serum-containing medium for over 24 h. However, the acutely isolated (less than 6 h from isolation) astrocytes, as well as acutely isolated astrocytes cultured in serum-free media, failed to respond to 5-HT by changes in Ca 1. Coinciding with the changes in Ca 1 levels, inward currents were activated by 10 μM 5-HT in cultured, but not in acutely isolated astrocytes. Two separate types of serotonin-induced, small-conductance inward single-channel currents were found. First, in both Ca 2+-containing and Ca 2+-free media serotonin transiently activated a small-conductance apamin-sensitive channel. Apamin is a specific blocker of the small-conductance Ca 2+-activated K + channel (sK Ca). When cells were pre-treated with phospholipase C inhibitor U73122 no 5-HT-induced sK Ca channel openings were seen, indicating that this channel was activated by Ca 2+ released from intracellular stores via IP 3. A second type of small inward channel activated later, but only in the presence of external Ca 2+. It was inhibited by the L-type Ca 2+ channel blockers, nimodipine and nifedipine. Both types of channel activity were inhibited by ketanserin, indicating activation of the 5-HT 2A receptor.