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Intracellular signal pathways controlling respiratory neurons
D W Richter1, P M Lalley, O Pierrefiche
1Department of Neurophysiology, University of Göttingen, Germany. dwr@neuro-physiol.med.uni-goettingen.de
Abstract:
Medullary respiratory neurons are influenced by a variety of neuromodulators, but there is a lack of information about the specific intracellular signal pathways involved. In this report we describe the modulatory effects of the cyclic adenosine-triphosphate (cAMP)-dependent protein kinase and of protein kinase C pathways on voltage- and ligand-controlled ionic conductances and demonstrate their functional significance in regulating the excitability of medullary respiratory neurons of the vivo cat. Evidence is presented that PKA and PKC pathways are persistently activated. PKA regulates current flow through persistently activated and GABAB receptor-controlled potassium channels as well as GABAA receptor-controlled chloride channels. PKC also depresses persistent potassium currents but it potentiates excitatory and inhibitory synaptic currents. The clinical significance of these intracellular signal pathways is demonstrated in a case of a child suffering from apneustic breathing, who was successfully treated with a 5HT-1A receptor agonist.
Insights
Intracellular signaling pathways, including protein kinase A (PKA) and protein kinase C (PKC), modulate respiratory neuron activity. These pathways are crucial for regulating breathing patterns and have clinical implications for respiratory disorders.
Area of Science:
- Neuroscience
- Respiratory Physiology
- Cellular Signaling
Background:
- Medullary respiratory neurons control breathing.
- Neuromodulators influence these neurons, but intracellular pathways are poorly understood.
Purpose of the Study:
- To investigate the role of cyclic adenosine-triphosphate (cAMP)-dependent protein kinase (PKA) and protein kinase C (PKC) pathways in medullary respiratory neurons.
- To elucidate the effects of these pathways on ionic conductances and neuronal excitability.
Main Methods:
- Electrophysiological recordings in vivo in cats.
- Analysis of voltage- and ligand-controlled ionic conductances.
- Assessment of PKA and PKC pathway activation and function.
Main Results:
- PKA and PKC pathways are persistently activated in medullary respiratory neurons.
- PKA modulates potassium and chloride channels, while PKC affects potassium currents and synaptic currents.
- These pathways are functionally significant in regulating neuronal excitability.
Conclusions:
- PKA and PKC are key intracellular signaling pathways regulating medullary respiratory neuron function.
- Dysregulation or modulation of these pathways can impact breathing control.
- Successful treatment of apneustic breathing with a 5HT-1A agonist highlights the clinical relevance.