SEROTONIN INDUCES INWARD POTASSIUM AND CALCIUM CURRENTS IN RAT CORTICAL ASTROCYTES

Ca2+ 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 mu M serotonin caused a transient increase in intracellular calcium (Ca-i) levels in fura-2AM-Ioaded cultured astrocytes and in as trocytes acutely isolated and then cultured in horse serum-containing medium for over 24 h. However, the acutely isolated (less than 6 h fro m isolation) astrocytes, as well as acutely isolated astrocytes cultur ed in serum-free media, failed to respond to 5-HT by changes in Ca-i. Coinciding with the changes in Ca-i levels, inward currents were activ ated by 10 mu M 5-HT in cultured, but not in acutely isolated astrocyt es. Two separate types of serotonin-induced, small-conductance inward single-channel currents were found. First, in both Ca2+-containing and Ca2+-free media serotonin transiently activated a small-conductance a pamin-sensitive channel. Apamin is a specific blocker of the small-con ductance Ca2+-activated K+ channel (sK(Ca)). When cells were pre-treat ed with phospholipase C inhibitor U73122 no 5-HT-induced sK(CA) channe l openings were seen, indicating that this channel was activated by Ca 2+ released from intracellular stores via IP3. A second type of small inward channel activated later, but only in the presence of external C a2+. It was inhibited by the L-type Ca2+ channel blockers, nimodipine and nifedipine. Both types of channel activity were inhibited by ketan serin, indicating activation of the 5-HT2A receptor.