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TASK‐like K + channels mediate effects of 5‐HT and extracellular pH in rat dorsal vagal neurones in vitro
Author(s) -
Hopwood Sarah E.,
Trapp Stefan
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.093070
Subject(s) - extracellular , chemistry , biophysics , depolarization , patch clamp , electrophysiology , postsynaptic potential , reversal potential , inhibitory postsynaptic potential , voltage clamp , neuroscience , current clamp , serotonergic , receptor , biochemistry , serotonin , membrane potential , biology
Dorsal vagal neurones (DVN) receive serotonergic projections from the medullary raphé nuclei, suggesting that 5‐HT modulates vagal activity. A previous study has shown that 5‐HT excites DVN in part by inhibition of a K + current via postsynaptic 5‐HT 2A receptors. As mRNA for the two‐pore‐domain K + channels TASK‐1 (KCNK3) and TASK‐3 (KCNK9) has been found in DVN, we investigated the possibility that 5‐HT exerts its effects via inhibition of these K + channels using whole‐cell patch‐clamp techniques. In current clamp, 5‐HT (20 μ m ) elicited a depolarization by 5.1 ± 1.5 mV and an increase in firing rate. In voltage clamp, 5‐HT reduced the standing outward current ( I SO ) at −20 mV by 106 ± 17 pA, inhibiting a conductance (reversal, −95 ± 4 mV) which displayed Goldman‐Hodgkin‐Katz outward rectification, supportive of a TASK‐like K + current. Since TASK channels are modulated by extracellular pH (pH o ), we next investigated the pH sensitivity of I SO in Hepes‐buffered ACSF. At pH o 7.3, DVN exhibited an I SO of 147 ± 15 pA at −20 mV. Acidification to pH o 6.3 reduced I SO to 85 ± 13 pA, whereas raising pH o to 8.5 increased I SO to 216 ± 26 pA. At pH o 7.3, I SO was inhibited by BaCl 2 (IC 50 465 μ m ), but unaffected by ZnCl 2 (100 μ m ). 5‐HT (10 μ m ) reduced I SO by 114 ± 17 pA at pH o 7.3, but at pH o 6.3 the 5‐HT‐induced inhibition of I SO was significantly smaller. The present data suggest that the excitatory effects of 5‐HT on DVN are mediated in part by inhibition of a TASK‐like, pH‐sensitive K + conductance. The pharmacological profile of this conductance excludes TASK‐3 homomers, but rather implicates TASK‐1‐containing channels.