Regulation of the chemosensory control of breathing by Kölliker-Fuse neurons

Am J Physiol Regul Integr Comp Physiol. 2014 Jul 1;307(1):R57-67. doi: 10.1152/ajpregu.00024.2014. Epub 2014 Apr 23.

Abstract

The Kölliker-Fuse region (KF) and the lateral parabrachial nucleus (LPBN) have been implicated in the maintenance of cardiorespiratory control. Here, we evaluated the involvement of the KF region and the LPBN in cardiorespiratory responses elicited by chemoreceptor activation in unanesthetized rats. Male Wistar rats (280-330 g; n = 5-9/group) with bilateral stainless-steel guide cannulas implanted in the KF region or the LPBN were used. Injection of muscimol (100 and 200 pmol/100 nl) in the KF region decreased resting ventilation (1,140 ± 68 and 978 ± 100 vs. saline: 1,436 ± 155 ml·kg(-1)·min(-1)), without changing mean arterial pressure (MAP) and heart rate (HR). Bilateral injection of the GABA-A antagonist bicuculline (1 nmol/100 nl) in the KF blocked the inhibitory effect on ventilation (1,418 ± 138 vs. muscimol: 978 ± 100 ml·kg(-1)·min(-1)) elicited by muscimol. Muscimol injection in the KF reduced the increase in ventilation produced by hypoxia (8% O2) (1,827 ± 61 vs. saline: 3,179 ± 325 ml·kg(-1)·min(-1)) or hypercapnia (7% CO2) (1,488 ± 277 vs. saline: 3,539 ± 374 ml·kg(-1)·min(-1)) in unanesthetized rats. Bilateral injection of bicuculline in the KF blocked the decrease in ventilation produced by muscimol in the KF during peripheral or central chemoreflex activation. Bilateral injection of muscimol in the LPBN did not change resting ventilation or the increase in ventilation elicited by hypoxia or hypercapnia. The results of the present study suggest that the KF region, but not the LPBN, has mechanisms to control ventilation in resting, hypoxic, or hypercapnic conditions in unanesthetized rats.

Keywords: Kölliker-Fuse; cardiorespiratory responses; chemoreflex; lateral parabrachial nucleus.

MeSH terms

  • Animals
  • Bicuculline / administration & dosage
  • Blood Pressure
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / metabolism*
  • Disease Models, Animal
  • GABA-A Receptor Agonists / administration & dosage
  • GABA-A Receptor Antagonists / administration & dosage
  • Heart Rate
  • Hypercapnia / metabolism
  • Hypercapnia / physiopathology
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Male
  • Muscimol / administration & dosage
  • Pons / drug effects
  • Pons / metabolism*
  • Pons / physiopathology
  • Rats
  • Rats, Wistar
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism
  • Reflex
  • Respiration* / drug effects
  • Signal Transduction* / drug effects
  • Time Factors

Substances

  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Receptors, GABA
  • Muscimol
  • Bicuculline