Gain modulation of respiratory neurons. Respir Physiol Neurobiol 2002 Jul;131(1-2):121-33
Date
07/11/2002Pubmed ID
12107000DOI
10.1016/s1569-9048(02)00042-3Scopus ID
2-s2.0-0036302432 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
A possible mechanism underlying adaptive control of the respiratory system is gain modulation of the discharge frequency (F(n)) patterns of medullary respiratory neurons mediated by GABA(A) receptors. Antagonism of GABA(A) receptors with bicuculline results in an F(n) pattern that is an amplified replica of the underlying control pattern. The contours of F(n) patterns remain proportional to one another. Studies suggest that a tonic GABA(A)ergic input constrains the control- and reflexly-induced activities of these neurons to about 35-50% of the discharge rate without this inhibitory input. The pharmacology of this mechanism is unusual in that picrotoxin, a noncompetitive GABA(A) receptor antagonist, does not produce gain modulation, but is able to block the silent phase inhibition (e.g. E phase of an I neuron). Alterations in the amplitude of spike afterhyperpolarizations mediated by Ca(2+) activated K(+) channels also produces gain modulation. This mechanism modulates exogenously- and endogenously-induced neuronal activities, whereas the bicuculline-sensitive GABAergic mechanism modulates only the respiratory-related activities. Thus, these two forms of gain modulation, acting in cascade manner, may provide robust mechanisms for the optimal control of respiratory, as well as other behavioral functions (e.g. coughing, sneezing, vomiting) mediated by respiratory premotor neurons.
Author List
Zuperku EJ, McCrimmon DRAuthor
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptation, PhysiologicalAnimals
GABA Antagonists
Humans
Medulla Oblongata
Models, Neurological
Motor Neurons
Receptors, GABA-A
Respiratory Mechanics
Signal Transduction
