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Gain modulation of respiratory neurons
Edward J Zuperku1, Donald R McCrimmon
1Research Service/151, Zablocki VA Medical Center, Milwaukee, WI 53295, USA. ezuperku@mcw.edu
Respiratory Physiology & Neurobiology
|July 11, 2002
Summary
Two mechanisms, GABA(A) receptor activity and calcium-activated potassium channels, modulate respiratory neuron firing rates. These processes, acting in cascade, ensure precise control of breathing and related behaviors.
Area of Science:
- Neuroscience
- Respiratory Physiology
- Pharmacology
Background:
- Adaptive control of the respiratory system relies on precise regulation of medullary respiratory neuron activity.
- GABA(A) receptors are implicated in modulating the discharge frequency (F(n)) patterns of these neurons.
Purpose of the Study:
- To investigate the mechanisms of gain modulation in medullary respiratory neurons.
- To elucidate the roles of GABA(A) receptors and calcium-activated potassium channels in respiratory control.
Main Methods:
- Pharmacological antagonism of GABA(A) receptors using bicuculline and picrotoxin.
- Analysis of discharge frequency (F(n)) patterns and spike afterhyperpolarizations.
Main Results:
- Bicuculline antagonism of GABA(A) receptors amplified F(n) patterns while maintaining proportionality.
- Tonic GABA(A)ergic input was found to constrain neuronal activity.
- Picrotoxin blocked silent phase inhibition but did not cause gain modulation.
- Modulation of calcium-activated potassium channels also induced gain modulation.
Conclusions:
- Two distinct gain modulation mechanisms, one GABA(A)ergic and another involving calcium-activated potassium channels, operate in a cascade.
- These mechanisms provide robust control for respiratory functions and related behaviors like coughing and sneezing.