Kelly Banagan
Advisor:  Dr. Joe Erlichman
SLU Festival of Science 2001 Poster Presentation
 
The Ventilatory Effects of Sodium/Hydrogen Exchange Inhibition
in the Nucleus Tractus  Solitarius
 
Abstract:
 
The brain stem is the principal site of carbon dioxide sensing in the brain.  The chemoreceptive regions are pH sensitive and regulate ventilatory responses to hypercapnia.  The sodium hydrogen exchanger (NHE) is believed to be the membrane transporter that regulates the intracellular pH (pHi) in one chemosensitive site, the Nucleus Tractus Solitarius (NTS), located in the dorsal medulla. Previous studies in vivo have shown that the NTS plays an important role in central respiratory control.  There are five known isoforms of NHE.  The NHE isoforms differ in tissue distribution, kinetics, and their response to external stimuli.  Isoform 1 (NHE1) and isoform 3 (NHE3) are widely distributed throughout the brainstem and may be the prominent protein transport systems permitting recovery from acid loads.  NHE1 is the dominant Na+/H+ exchanger in the plasma membrane, and is believed to work with cytosolic NHE3 in the regulation of pHi.  Previous studies, utilizing immunohistochemical techniques, have shown that NHE3 is sparsely distributed throughout the medulla.  Previous studies have also shown that the inhibition of NHE3 acidified the pHi of neurons on the ventral medullary surface located in chemosensitive regions, without affecting the glia.  In this study I examined the ventilatory effects of selective inhibition of NHE using HOE 642, a selective NHE1 inhibitor, and S1611, a selective NHE3 inhibitor.  Adult rats were cannulated unilaterally in the NTS. Animals were exposed to progressive hypercapnia while ventilation was measured using a whole-body plesmograph.  I found that there were no significant ventilatory effects with focal inhibition of the NHE1 and NHE3 sodium isoforms in the conscious rat.  These findings suggest two possibilities.  First, NHE1 and NHE3 may work in conjunction with each other such that both transporters must be blocked for pHi regulation to be impaired.  Second, it is possible that a different NHE isoform may predominant in this region of the brain.