| 16800867 |
Zhao MG, Hulsmann S, Winter SM, Dutschmann M, Richter DW: Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition. Eur J Neurosci. 2006 Jul;24(1):145-54. Epub 2006 Jun 26.
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-Botzinger 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. |
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