IN SEARCH OF THE REAL RESPIRATORY NEURONS - CULTURE OF MEDULLARY FETAL CELLS SENSITIVE TO CO2 AND LOW PH

Although extensively pursued, the real respiratory neurons have remain ed elusive. We departed from the more conventional physiologic and mor phologic methods of system and tissue examination and cultured dissoci ated fetal rat cells from the areas of the nucleus ambiguus and the nu cleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, stud ied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in ampl itude. Other irregularly beating or silent cells did not respond or el se required very large pulses (>200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosul fite with an increase in spike frequency and amplitude; high oxygen (> 600 Torr) and adenosine produced a decrease in electrical activity. Mo st of these cells were multipolar after staining with antibodies to ne uron-specific enolase and fragment C of tetanus toxin. They did not st ain for choline acetyltransferase. The results suggest that these cult ured cells, expressing a phenotype inherently responsive to CO2 and lo w pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm.