title: Cardiorespiratory effects of gap junction blockade in the locus coeruleus in unanesthetized adult rats.
abstract: The locus coeruleus (LC) plays an important role in central chemoreception. In young rats (P9 or younger), 85% of LC neurons increase firing rate in response to hypercapnia vs. only about 45% of neurons from rats P10 or older. Carbenoxolone (CARB - gap junction blocker) does not affect the % of LC neurons responding in young rats but it decreases the % responding by half in older animals. We evaluated the participation of gap junctions in the CO2 ventilatory response in unanesthetized adult rats by bilaterally microinjecting CARB (300μM, 1mM or 3mM/100nL), glycyrrhizic acid (GZA, CARB analog, 3mM) or vehicle (aCSF - artificial cerebrospinal fluid) into the LC of Wistar rats. Bilateral gap junction blockade in LC neurons did not affect resting ventilation; however, the increase in ventilation produced by hypercapnia (7% CO2) was reduced by ∼25% after CARB 1mM or 3mM injection (1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1468.3±122.2mLkg(-1)min(-1) for 1mM CARB, P<0.05; 1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1540.9±68.4mLkg(-1)min(-1) for the 3mM CARB group, P<0.05) due largely to a decrease in respiratory frequency. GZA injection or CARB injection outside the LC (peri-LC) had no effect on ventilation under any conditions. The results suggest that gap junctions in the LC modulate the hypercapnic ventilatory response of adult rats.
authors.affiliation: Department of Animal Physiology and Morphology, Sao Paulo State University- UNESP/FCAV, Jaboticabal, SP, Brazil; National Institute of Science and Technology in Comparative Physiology (INCT, Fisiologia Comparada), Brazil.
authors.forename: Luis G A
authors.initials: LG
authors.lastname: Patrone
authors.forename: Kênia Cardoso
authors.initials: KC
authors.lastname: Bícego
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Hartzler
authors.forename: Robert W
authors.initials: RW
authors.lastname: Putnam
authors.forename: Luciane H
authors.initials: LH
authors.lastname: Gargaglioni
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents; D001784:Blood Gas Analysis; D002229:Carbenoxolone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006935:Hypercapnia / Q000503:physiopathology; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D014851:Wakefulness / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D019695:Glycyrrhizic Acid; D002229:Carbenoxolone
keywords: A6; Carbenoxolone; Electrical coupling; Hypercapnia; Ventilation