Modulation of the hypoxic ventilatory response by Ca2+-dependent and Ca2+-independent protein kinase C in the dorsocaudal brainstem of conscious rats.
Protein kinase C (PKC) activation in the nucleus tractus solitarii (NTS) is critical for mounting an appropriate hypoxic ventilatory response (HVR). Furthermore, hypoxia elicits translocation of both Ca2+-dependent and Ca2+-independent PKC isoforms in the NTS. However, the relative functional contribution of such PKC isoforms in mediating HVR is unclear. To study these issues, chronically instrumented adult Sprague-Dawley rats underwent hypoxic challenges (10% O2 balance in N2) following dorsocaudal brainstem microinjections of the selective Ca2+-dependent PKC inhibitor Gö 6976 (10 mmol in 1 microl). Compared with vehicle, Gö 6976 did not modify normoxic ventilation but maximally attenuated HVR by 38.4 +/- 6.7% (n = 9; P < 0.01), with similar contributions from tidal volume and respiratory frequency. In seven additional animals, when the non Ca2+-selective PKC blocker BIM I was concurrently microinjected with Gö 6976, further reductions in peak ventilatory responses to hypoxia occurred (P < 0.04). When BIM V, the inactive analog, was microinjected with Gö 6976, the magnitude of HVR attenuation was unchanged (n = 6; Gö 6976 vs. Gö 6976 + BIM V: P = NS). We conclude that in the dorsocaudal brainstem, PKC-mediated components of HVR involve activation of both Ca2+-dependent and Ca2+-independent PKC isoforms.
Gozal
D
D
Department of Pediatrics (SL-37), Tulane University School of Medicine, New Orleans, LA 70112, USA. dgozal@tmcpop.tmc.tulane.edu
Graff
G R
GR
Gozal
E
E
Torres
J E
JE
D000818:Animals; D001784:Blood Gas Analysis; D001933:Brain Stem / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; C081021:Go 6976; D011493:Protein Kinase C; D002118:Calcium