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 microM serotonin caused a transient increase in intracellular calcium (Ca(i)) 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(i). Coinciding with the changes in Ca(i) levels, inward currents were activated by 10 microM 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 Ca2+-containing and Ca2+-free media serotonin transiently activated a small-conductance apamin-sensitive channel. Apamin is a specific blocker of the small-conductance Ca2+-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 Ca2+ released from intracellular stores via IP3. A second type of small inward channel activated later, but only in the presence of external Ca2+. It was inhibited by the L-type Ca2+ channel blockers, nimodipine and nifedipine. Both types of channel activity were inhibited by ketanserin, indicating activation of the 5-HT2A receptor.
Jalonen
T O
TO
Division of Neurosurgery, Albany Medical College, NY 12208, USA.
Margraf
R R
RR
Wielt
D B
DB
Charniga
C J
CJ
Linne
M L
ML
Kimelberg
H K
HK
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004594:Electrophysiology; D017136:Ion Transport / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D012701:Serotonin