Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition.
Mutant oscillator mice (Glra1(spd -/-)) 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.
Zhao
Ming-Gao
MG
Department of Neuro- and Sensory Physiology, Georg-August-University Göttingen, Humboldtallee 23, 37073 Göttingen.
Hülsmann
Swen
S
Winter
Stefan M
SM
Dutschmann
Mathias
M
Richter
Diethelm W
DW
D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D002118:Calcium / Q000502:physiology*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010507:Periodicity; D012143:Respiratory Physiological Phenomena; D013331:Strychnine / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; C064719:iberiotoxin; D013331:Strychnine; D002118:Calcium