Modulation of the hypoxic ventilatory response by Ca2+-dependent and Ca2+-independent protein kinase C in the dorsocaudal brainstem of conscious rats

D. Gozal, G. R. Graff, E. Gozal, J. E. Torres

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 Go 6976 (10 mmol in 1 μl). Compared with vehicle, Go 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 Go 6976, further reductions in peak ventilatory responses to hypoxia occurred (P<0.04). When BIM V, the inactive analog, was microinjected with Go 6976, the magnitude of HVR attenuation was unchanged (n=6; Go 6976 vs. Go 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. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalRespiration Physiology
Volume112
Issue number3
DOIs
StatePublished - Jun 1 1998

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine

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