TASK-like K super(+) channels mediate effects of 5-HT and extracellular pH in rat dorsal vagal neurones in vitro

• Published in: The Journal of physiology 2005-10, Vol.568 (1), p.145-154
• Main Authors: Hopwood, Sarah E, Trapp, Stefan
• Format: Article
• Language: English
• ISSN: 0022-3751

Dorsal vagal neurones (DVN) receive serotonergic projections from the medullary raphe 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 super(+) current via postsynaptic 5-HT sub(2A) receptors. As mRNA for the two-pore-domain K super(+) 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 super(+) channels using whole-cell patch-clamp techniques. In current clamp, 5-HT (20 mu M) elicited a depolarization by 5.1 plus or minus 1.5 mV and an increase in firing rate. In voltage clamp, 5-HT reduced the standing outward current (I sub(SO)) at -20 mV by 106 plus or minus 17 pA, inhibiting a conductance (reversal, -95 plus or minus 4 mV) which displayed Goldman-Hodgkin-Katz outward rectification, supportive of a TASK-like K super(+) current. Since TASK channels are modulated by extracellular pH (pH sub(o)), we next investigated the pH sensitivity of I sub(SO) in Hepes-buffered ACSF. At pH sub(o) 7.3, DVN exhibited an I sub(SO) of 147 plus or minus 15 pA at -20 mV. Acidification to pH sub(o) 6.3 reduced I sub(SO) to 85 plus or minus 13 pA, whereas raising pH sub(o) to 8.5 increased I sub(SO) to 216 plus or minus 26 pA. At pH sub(o) 7.3, I sub(SO) was inhibited by BaCl sub(2) (IC sub(50) 465 mu M), but unaffected by ZnCl sub(2) (100 mu M). 5-HT (10 mu M) reduced I sub(SO) by 114 plus or minus 17 pA at pH sub(o) 7.3, but at pH sub(o) 6.3 the 5-HT-induced inhibition of I sub(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 super(+) conductance. The pharmacological profile of this conductance excludes TASK-3 homomers, but rather implicates TASK-1-containing channels.