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Endogenous rhythm generation in the pre-Bötzinger complex and ionic currents: modelling and in vitro studies
Ilya A Rybak1, Natalia A Shevtsova, Walter M St-John
1School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA. rybak@cbis.ece.drexel.edu
The European Journal of Neuroscience
|July 31, 2003
Summary
The pre-Bötzinger complex generates respiratory rhythms. Suppressing potassium currents or augmenting persistent sodium currents in computational models and in vitro rat brainstem slices induced rhythmic bursting activity, crucial for breathing.
Area of Science:
- Neuroscience
- Computational Neuroscience
- Respiratory Physiology
Background:
- The pre-Bötzinger complex (preBötC) is essential for generating the respiratory rhythm in mammals.
- In vitro studies show the preBötC can exhibit endogenous rhythmic bursting activity under specific conditions.
Purpose of the Study:
- To investigate the conditions that induce endogenous bursting activity in the preBötC.
- To computationally model preBötC pacemaker neurons and experimentally validate model predictions.
Main Methods:
- Developed a Hodgkin-Huxley style computational model of preBötC pacemaker neurons, incorporating persistent sodium and delayed-rectifier potassium currents.
- Analyzed the model's firing behavior under varying current expressions.
- Recorded endogenous population activity from in vitro neonatal rat brainstem slices and hypoglossal nerve activity.
Main Results:
- Computational models predicted that suppressing delayed-rectifier potassium current or augmenting persistent sodium current induces bursting.
- In vitro experiments confirmed that elevated extracellular potassium or application of potassium channel blockers triggered rhythmic activity.
- This activity was abolished by blocking persistent sodium current with riluzole.
Conclusions:
- The expression of persistent sodium and delayed-rectifier potassium currents critically influences preBötC bursting.
- Experimental findings support computational predictions regarding the ionic mechanisms underlying preBötC rhythmic activity.
- Understanding these mechanisms is vital for comprehending respiratory rhythm generation in vivo and during altered physiological states like gasping.