Project Details


The ventilatory responses to respiratory and metabolic acid-base
disturbances are primarily mediated through stimulation of the central
chemoreceptors which are thought to be located close to the surface of the
ventrolateral medulla. Characterization of central chemosensitivity has
heretofore been obtained primarily from intact preparations which do not
allow distinction to be made between primary chemosensitive cells and those
which are secondarily excited. The general objective of this proposal is
to define the stimulus-response characteristics of individual
chemosensitive neurons by using tissue culture techniques. This approach
has been successfully utilized for the characterization of thermosensitive
neurons in the hypothalamus. Preliminary studies using these techniques on
ventral medullary tissue have shown that acid-sensitive neurons are readily
identifiable in tissue culture. Three hypotheses regarding the nature of chemosensitivity in tissue culture
are proposed for study. (1) It is proposed that acid sensitivity in tissue
culture is specific to ventral medulla. This will be tested by comparing
the stimulus-response characteristics of spontaneously active neurons in
ventral and dorsal medullary tissue cultures. (2) It is proposed that a
portion of the ventral medullary neurons are intrinsically ("primarily")
acid sensitive. This will be tested by determining whether
chemosensitivity persists in some neurons after blockade of synaptic
transmission (high Mg++-low Ca++ perfusate). (3) It is proposed that
acetylcholine and opiates modulate the acid sensitivity of chemosensitive
neurons. This will be tested by determining the effect of agonists and
antagonists of ACh and opiates on the stimulus response of acid-sensitive
neurons. Studies will be performed on 21-35 day tissue cultures prepared
from ventral and dorsal medullary tissue of newborn rats. Extracellular
recordings will be made while the perfusate pH is randomly varied by either
altering PCO2 at constant HCO3- or altering (HCO3-) at constant PCO2.
Automated data collection will allow computation of linear regression of
neuronal firing rate and ECF pH.
Effective start/end date9/30/862/28/90


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)

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