Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats

Am J Physiol Regul Integr Comp Physiol. 2013 Oct 1;305(7):R780-92. doi: 10.1152/ajpregu.00029.2013. Epub 2013 Aug 15.

Abstract

The effect of hypercapnia on outwardly rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)-P15]. Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6 mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n = 5) in 15% CO2 [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO2 (pHo 7.00, pHi 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate, but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pHo or pHi. The change of the A current by various levels of CO2 is correlated with the change in firing rate induced by CO2, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons.

Keywords: A current; carbon dioxide; central control of breathing; neuronal acid sensing; potassium channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / metabolism
  • Acidosis / physiopathology
  • Animals
  • Animals, Newborn
  • Carbon Dioxide / metabolism*
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / metabolism*
  • Evoked Potentials
  • Hydrogen-Ion Concentration
  • Hypercapnia / metabolism
  • Hypercapnia / physiopathology
  • Hypocapnia / metabolism
  • Hypocapnia / physiopathology
  • In Vitro Techniques
  • Kinetics
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism*
  • Locus Coeruleus / physiopathology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Potassium Channel Blockers
  • Potassium Channels
  • Carbon Dioxide