title: Focal CO2/H+ alters phrenic motor output response to chemical stimulation of cat pre-Botzinger complex in vivo.
abstract: Microinjection of dl-homocysteic acid (DLH), a glutamate analog, into the pre-Bötzinger complex (pre-BötC) can produce tonic excitation of phrenic nerve discharge. Although this DLH-induced tonic excitation can be modified by systemic hypercapnia, the role of focal increases in pre-BötC CO(2)/H(+) in this modulation of the DLH-induced response remains to be determined. Therefore, we examined the effects of unilateral microinjection of DLH (10 mM; 10-20 nl) into the pre-BötC before and during increased focal pre-BötC CO(2)/H(+) (i.e., focal tissue acidosis) in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Focal tissue acidosis was produced by blockade of carbonic anhydrase with either focal acetazolamide (AZ) or methazolamide (MZ) microinjection. For these experiments, sites were selected in which unilateral microinjection of DLH into the pre-BötC produced a nonphasic tonic excitation of phrenic nerve discharge (n = 10). Microinjection of 10-20 nl AZ (50 microM) or MZ (50 microM) into these 10 sites in the pre-BötC increased the amplitude and/or frequency of eupneic phrenic bursts, as previously reported. Subsequent microinjection of DLH produced excitation in which phasic respiratory bursts were superimposed on tonic discharge. These DLH-induced phasic respiratory bursts had an increased frequency compared with the preinjection baseline frequency (P < 0.05). These findings demonstrate that modulation of phrenic motor activity evoked by DLH-induced activation of the pre-BötC is influenced by focal CO(2)/H(+) chemosensitivity in this region. Furthermore, these findings suggest that focal increases in pre-BötC CO(2)/H(+) may have contributed to the modulation of the DLH-induced responses previously observed during systemic hypercapnia.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794-8661, USA. icsolomon@physiology.pnb.sunysb.edu
authors.forename: Irene C
authors.initials: IC
authors.lastname: Solomon
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002415:Cats; D006710:Homocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology*; D008845:Microinjections; D009043:Motor Activity; D010791:Phrenic Nerve / Q000503:physiopathology*; D011522:Protons
chemical_list: D011522:Protons; D006710:Homocysteine; C007956:homocysteic acid; D002245:Carbon Dioxide