Evidence for TREK-like tandem-pore domain channels in intrapulmonary chemoreceptor chemotransduction.
Intrapulmonary chemoreceptors (IPC) are carbon dioxide sensing neurons that innervate the lungs of birds, control breathing pattern, and are inhibited by halothane and intracellular acidosis. TASK and TREK are subfamilies of tandem-pore domain potassium leak channels, important in setting resting membrane potential, that are affected by volatile anesthetics and acidosis. We hypothesized that such channels might underlie signal transduction in IPC. We treated mallard ducks with four volatile anesthetics in increasing concentrations to test their effects on IPC discharge through single cell, extracellular recording from vagal fibers. Isoflurane inhalation attenuated IPC discharge only at 8.25% inspired (alpha=0.05). Halothane attenuated IPC discharge significantly (alpha=0.05) at all treatment levels. Chloroform at 3.8%, 5.6%, and 8.25% significantly attenuated IPC discharge (alpha=0.05). Ether at 1.9%, 2.9%, and 3.8% significantly attenuated IPC discharge (alpha=0.05), abolishing IPC discharge at 3.8% inspired. The pharmacological signature of IPC discharge attenuation suggests that IPC express tandem-pore domain leak channels similar to TREK channels, which are inhibited by intracellular acidosis.
Bina
Robert Wagner
RW
Department of Biology, Northern Arizona University, Franklin and Beaver Streets, Flagstaff, AZ 86011-5640, USA. robert.bina@asu.edu
Hempleman
Steven C
SC
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D002725:Chloroform / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004372:Ducks; D004986:Ether / Q000008:administration & dosage; D005260:Female; D006221:Halothane / Q000008:administration & dosage; D007530:Isoflurane / Q000008:administration & dosage; D008168:Lung / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018685:Anesthetics, Inhalation; D024683:Potassium Channels, Tandem Pore Domain; D011956:Receptors, Cell Surface; C054079:carbon dioxide receptor; C103742:potassium channel protein TREK-1; D004986:Ether; D002725:Chloroform; D007530:Isoflurane; D006221:Halothane