CO2/H+ chemoreception in the cat pre-Botzinger complex in vivo

We examined the effects of focal tissue acidosis in the pre-Botzinger compl ex (pre-BotC; the proposed locus of respiratory rhythm generation) on phren ic nerve discharge in chloralose-anesthetized, vagotomized, paralyzed, mech anically ventilated cats. Focal tissue acidosis was produced by unilateral microinjection of 10-20 nl of the carbonic anhydrase inhibitors acetazolami de (AZ; 50 mu M) or methazolamide (MZ; 50 mu M). Microinjection of AZ and M Z into 14 sites in the pre-BotC reversibly increased the peak amplitude of integrated phrenic nerve discharge and, in some sites, produced augmented b ursts (i.e., eupneic breath ending with a high-amplitude, short-duration bu rst). Microinjection of AZ and MZ into this region also reversibly increase d the frequency of eupneic phrenic bursts in seven sites and produced prema ture bursts (i.e., doublets) in five sites. Phrenic nerve discharge increas ed within 5-15 min of microinjection of either agent; however, the time to the peak increase and the time to recovery were less with AZ than with MZ, consistent with the different pharmacological properties of AZ and MZ. In c ontrast to other CO2/H+ brain stem respiratory chemosensitive sites demonst rated in vivo, which have only shown increases in amplitude of integrated p hrenic nerve activity, focal tissue acidosis in the pre-BotC increases freq uency of phrenic bursts and produces premature (i.e., doublet) bursts. Thes e data indicate that the pre-BotC has the potential to play a role in the m odulation of respiratory rhythm and pattern elicited by increased CO2/H+ an d lend additional support to the concept that the proposed locus for respir atory rhythm generation has intrinsic chemosensitivity.