Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition

Authors

  • Ming-Gao Zhao,

    1. Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen
    Search for more papers by this author
    • *

      Present address: Department of Pharmacology, Fourth Military Medical University, no. 17 Changle West Road, Xi'an 710032, SHaanxi, P.R.China.

    • M.-G.Z. and S.H. contributed equally to this study.

  • Swen Hülsmann,

    1. Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen
    Search for more papers by this author
    • M.-G.Z. and S.H. contributed equally to this study.

  • Stefan M. Winter,

    1. Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen
    2. DFG Research Center for Molecular Biology of the Brain Humboldtallee 23, 37073 Göttingen
    Search for more papers by this author
  • Mathias Dutschmann,

    1. Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen
    Search for more papers by this author
  • Diethelm W. Richter

    1. Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen
    Search for more papers by this author

Dr S. Hülsmann and Dr D. W. Richter, as above.
E-mail: shuelsm2@uni-goettingen.de and d.richter@gwdg.de

Abstract

Mutant oscillator mice (Glra1spd –/–) are characterized by a developmental loss of glycinergic inhibition. These mice die during the third postnatal week presumably due to gradually increasing disturbances of breathing and motor behaviour. Some irregular rhythmic respiratory activity, however, is persevered until they die. Here we analysed cellular mechanisms that compensate for the loss of glycinergic inhibition and contribute to the maintenance of the respiratory rhythm. In a medullary slice preparation including the pre-Bötzinger complex we performed a comparative analysis of after-hyperpolarizations following action potentials (AP-AHP) and burst discharges (burst-AHP) in identified respiratory neurons from oscillator and control mice. Both AHP forms were increased in neurons from oscillator mice. These changes were combined with an augmented adaptation of firing frequency. Assuming that oscillator mice might upregulate calcium-activated K currents (BKCa) in compensation for the loss of glycinergic inhibition, we blocked the big KCa conductances with iberiotoxin and verified that the respiratory rhythm was indeed arrested by BK channel blockade.

Ancillary