Faculty Collaboration Database

Protein kinase C modulates ventilatory patterning in the developing rat. Am J Respir Crit Care Med 1999 Mar;159(3):968-73

Date

03/02/1999

Pubmed ID

10051280

DOI

10.1164/ajrccm.159.3.9805041

Scopus ID

2-s2.0-0032985146 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Protein kinase C (PKC) mediates important components of signal transduction pathways underlying neuronal excitability and modulates respiratory timing mechanisms in adult rats. To determine ventilatory effects of systemic PKC inhibition during development, whole-body plethysmographic recordings were conducted in 2-3-d (n = 11), 5-6-d (n = 19), 10-12-d (n = 14), and 20-21-d-old (n = 14) rat pups after treatment with vehicle and Ro 32-0432 (100 mg/kg, intraperitoneally). Ro 32-0432 decreased minute ventilation (V E) by 51.0 +/- 5.5% (mean +/- SEM) in youngest pups (p < 0.01) but only 19.1 +/- 6.8% in 20-21-d-old pups (p < 0.01). V E decreases were always due to frequency reductions with tidal volume (VT) remaining unaffected. Respiratory rate decreases primarily resulted from marked expiratory time (TE) prolongations being more pronounced in 2-3-d-old (115.5 +/- 28.9%) compared with 20-21-d old (36.6 +/- 10.9%; p < 0.002 analysis of variance [ANOVA] ). Expression of the PKC isoforms alpha, beta, gamma, delta, iota, and mu was further examined in brainstem and cortex by immunoblotting and revealed different patterns with postnatal age and location. We conclude that endogenous PKC inhibition elicits age-dependent ventilatory reductions which primarily affect timing mechanisms rather than changes in volume drive. This effect on ventilation abates with increasing postnatal age suggesting that the neural substrate mediating overall respiratory output may be more critically dependent on PKC activity in the immature animal.

Author List

Bandla HP, Simakajornboon N, Graff GR, Gozal D

Author

Hari Bandla MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Animals
Animals, Newborn
Blotting, Western
Brain Stem
Cerebral Cortex
Enzyme Inhibitors
Indoles
Plethysmography, Whole Body
Protein Kinase C
Pulmonary Ventilation
Pyrroles
Rats
Rats, Sprague-Dawley
Tidal Volume