RT Journal
A1 Sirois, Jay E.
A1 Lei, Qiubo
A1 Talley, Edmund M.
A1 Lynch, Carl
A1 Bayliss, Douglas A.
T1 The TASK-1 Two-Pore Domain K+ Channel Is a Molecular Substrate for Neuronal Effects of Inhalation Anesthetics
JF The Journal of Neuroscience 
JO The Journal of Neuroscience 
YR 2000 
FD September 01 
VO 20 
IS 17 
SP 6347 
OP 6354 
DO 10.1523/JNEUROSCI.20-17-06347.2000 
UL http://www.jneurosci.org/content/20/17/6347.abstract 
AB Despite widespread use of volatile general anesthetics for well over a century, the mechanisms by which they alter specific CNS functions remain unclear. Here, we present evidence implicating the two-pore domain, pH-sensitive TASK-1 channel as a target for specific, clinically important anesthetic effects in mammalian neurons. In rat somatic motoneurons and locus coeruleus cells, two populations of neurons that express TASK-1 mRNA, inhalation anesthetics activated a neuronal K+ conductance, causing membrane hyperpolarization and suppressing action potential discharge. These membrane effects occurred at clinically relevant anesthetic levels, with precisely the steep concentration dependence expected for anesthetic effects of these compounds. The native neuronal K+ current displayed voltage- and time-dependent properties that were identical to those mediated by the open-rectifier TASK-1 channel. Moreover, the neuronal K+ channel and heterologously expressed TASK-1 were similarly modulated by extracellular pH. The decreased cellular excitability associated with TASK-1 activation in these cell groups probably accounts for specific CNS effects of anesthetics: in motoneurons, it likely contributes to anesthetic-induced immobilization, whereas in the locus coeruleus, it may support analgesic and hypnotic actions attributed to inhibition of those neurons.