CO(2)/H(+) chemoreception in the cat pre-Bötzinger complex in vivo.
We examined the effects of focal tissue acidosis in the pre-Bötzinger complex (pre-BötC; the proposed locus of respiratory rhythm generation) on phrenic nerve discharge in chloralose-anesthetized, vagotomized, paralyzed, mechanically ventilated cats. Focal tissue acidosis was produced by unilateral microinjection of 10-20 nl of the carbonic anhydrase inhibitors acetazolamide (AZ; 50 microM) or methazolamide (MZ; 50 microM). Microinjection of AZ and MZ into 14 sites in the pre-BötC reversibly increased the peak amplitude of integrated phrenic nerve discharge and, in some sites, produced augmented bursts (i.e., eupneic breath ending with a high-amplitude, short-duration burst). Microinjection of AZ and MZ into this region also reversibly increased the frequency of eupneic phrenic bursts in seven sites and produced premature bursts (i.e., doublets) in five sites. Phrenic nerve discharge increased 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 contrast to other CO(2)/H(+) brain stem respiratory chemosensitive sites demonstrated in vivo, which have only shown increases in amplitude of integrated phrenic nerve activity, focal tissue acidosis in the pre-BötC increases frequency of phrenic bursts and produces premature (i.e., doublet) bursts. These data indicate that the pre-BötC has the potential to play a role in the modulation of respiratory rhythm and pattern elicited by increased CO(2)/H(+) and lend additional support to the concept that the proposed locus for respiratory rhythm generation has intrinsic chemosensitivity.
Solomon
I C
IC
Department of Physiology and Biophysics, State University of New York at Stony Brook, 11794-8661, USA. ICSolomon@physiology.pnb.sunysb.edu
Edelman
N H
NH
O'Neal
M H
MH
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002415:Cats; D002628:Chemoreceptor Cells / Q000502:physiology*; D004594:Electrophysiology; D006859:Hydrogen / Q000378:metabolism*; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D008704:Methazolamide / Q000494:pharmacology; D008845:Microinjections; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology
D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D006859:Hydrogen; D000086:Acetazolamide; D008704:Methazolamide