Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels

Am J Physiol Cell Physiol. 2003 Jan;284(1):C145-55. doi: 10.1152/ajpcell.00346.2002. Epub 2002 Sep 18.


We studied chemosensitive signaling in locus coeruleus (LC) neurons using both perforated and whole cell patch techniques. Upon inhibition of fast Na(+) spikes by tetrodotoxin (TTX), hypercapnic acidosis [HA; 15% CO(2), extracellular pH (pH(o)) 6.8] induced small, slow spikes. These spikes were inhibited by Co(2+) or nifedipine and were attributed to activation of L-type Ca(2+) channels by HA. Upon inhibition of both Na(+) and Ca(2+) spikes, HA resulted in a membrane depolarization of 3.52 +/- 0.61 mV (n = 17) that was reduced by tetraethylammonium (TEA) (1.49 +/- 0.70 mV, n = 7; P < 0.05) and absent (-0.97 +/- 0.73 mV, n = 7; P < 0.001) upon exposure to isohydric hypercapnia (IH; 15% CO(2), 77 mM HCO(3)(-), pH(o) 7.45). Either HA or IH, but not 50 mM Na-propionate, activated Ca(2+) channels. Inhibition of L-type Ca(2+) channels by nifedipine reduced HA-induced increased firing rate and eliminated IH-induced increased firing rate. We conclude that chemosensitive signals (e.g., HA or IH) have multiple targets in LC neurons, including TEA-sensitive K(+) channels and TWIK-related acid-sensitive K(+) (TASK) channels. Furthermore, HA and IH activate L-type Ca(2+) channels, and this activation is part of chemosensitive signaling in LC neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Calcium Channels / physiology*
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / physiology
  • Hypercapnia / physiopathology
  • In Vitro Techniques
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium Channels / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tetrodotoxin / pharmacology


  • Calcium Channels
  • Potassium Channels
  • Tetrodotoxin