Stabilization of bursting in respiratory pacemaker neurons.

  • Tryba A
  • Peña F
  • Ramirez J
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Synaptic and endogenous pacemaker properties have been hypothesized as principal cellular mechanisms for respiratory rhythm generation. This rhythmic activity is thought to originate in the pre-Bötzinger complex, an area that can generate fictive respiration when isolated in brainstem slice preparations of mice. In slice preparations, external potassium concentration ([K+]o) is typically elevated from 3 to 8 mm to induce rhythmic population activity. However, elevated [K+](o) may not simply depolarize respiratory neurons but also change rhythm-generating mechanisms by inducing or altering pacemaker properties. To test this, we examined the membrane potential (V(m)) of nonpacemaker neurons and endogenous bursting properties of pacemaker neurons before and after blockade of excitatory and inhibitory synaptic input in 3 mm [K+]o artificial CSF (aCSF). Most pacemaker neurons (82%) ceased to burst in 3 mm [K+]o aCSF after blockade of glutamatergic transmission. In all of these, endogenous bursting was restored on additional blockade of glycinergic and GABAergic inhibition. Thus, bursting properties are suppressed by endogenous synaptic inhibition, the level of which may determine whether network rhythmicity is generated in 3 mm (n = 12) or 8 mm (n = 40) [K+]o aCSF. In 3 mm [K+]o aCSF, synaptically isolated pacemaker neurons (n = 22) continued to burst over a wide range of imposed V(m). Furthermore, the V(m) of synaptically isolated pacemaker neurons was not significantly affected (p = 0.1; n = 10) when [K+]o was changed from 8 to 3 mm, whereas isolated nonpacemakers hyperpolarized (p < 0.001; n = 14). We conclude that respiratory pacemaker neurons possess membrane properties that stabilize their bursting against changes in [K+]o and imposed changes in V(m).

Author-supplied keywords

  • pacemaker properties
  • pattern generation
  • potassium concentration
  • pre-bo
  • respiration
  • rhythm generation
  • tzinger complex

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  • Andrew K. Tryba

  • Fernando Peña

  • Jan-Marino Ramirez

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