Abstract 1871 Pulmonary: Control of Breathing Poster Symposium, Tuesday, 5/4

We have previously identified pacemaker cells uniquely responsive to CO2 in the upper medulla of fetal rats, 2 mm rostral to the obex. These cells originated in the areas of the nucleus ambiguus and nucleus tractus solitarius (J. Neurosci. Res. 33:590-597, 1992). We believe these cells to be central chemoreceptors with possible involvement in the generation of breathing. In the present study, we have further characterized these cells by examining the response to various neurotransmitters thought to be involved in the respiratory response to hypoxia in vivo: glutamic acid and its antagonist MK801 (n=8), GABA and its antagonist bicuculline (n=6), adenosine and its antagonist theophylline (n=8). Pacemaker cells increased their spike frequency with glutamic acid by 82% (336±25 to 612±30; p<0.001) and this increase was reduced to 41% when administration of MK801 preceded glutamic acid. GABA invariably blocked the action of glutamic acid. GABA also depressed the baseline spike frequency by 34% (p<0.01) and this was blocked by bicuculline. Finally, adenosine did not alter the baseline spike frequency but theophylline increased it by 26% (132±18 spikes/min to 166±14; p<0.05). In all of the above, irregular breathing cells responded poorly and silent cells did not respond. The findings suggest that these unique cells respond to known neurotransmitters involved in the response to hypoxia in a manner similar to that observed in vivo. We speculate that these pacemaker cells represent that basic cellular unit of the central respiratory network.

Supported by The Children's Hospital of Manitoba Inc.