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Protein kinase C modulates ventilatory patterning in the developing rat
H P Bandla1, N Simakajornboon, G R Graff
1Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of Pediatrics and Physiology, and Inter-Departmental Neuroscience and Cellular and Molecular Biology Programs, Tulane University School of Medicine, New Orleans, LA, USA.
Summary
Systemic inhibition of Protein Kinase C (PKC) reduces ventilation in developing rat pups, primarily by altering respiratory timing. This effect diminishes with age, indicating PKC
Area of Science:
- Neuroscience
- Developmental Biology
- Respiratory Physiology
Background:
- Protein Kinase C (PKC) is crucial for neuronal excitability and respiratory control in adult animals.
- Understanding PKC's role in developing respiratory systems is essential for identifying maturational vulnerabilities.
Purpose of the Study:
- To investigate the ventilatory effects of systemic Protein Kinase C inhibition during postnatal development in rat pups.
- To determine age-dependent changes in respiratory responses to PKC inhibition.
Main Methods:
- Whole-body plethysmography was used to record ventilation in rat pups of different postnatal ages (2-3, 5-6, 10-12, and 20-21 days).
- Rat pups were treated with Ro 32-0432, a PKC inhibitor, or vehicle.
- Immunoblotting was employed to analyze the expression patterns of various PKC isoforms in the brainstem and cortex.
Main Results:
- PKC inhibition significantly decreased minute ventilation (VE) in all age groups, with the most pronounced reduction observed in the youngest pups (2-3 days old).
- Ventilation reduction was primarily due to a decrease in respiratory frequency, not tidal volume, driven by prolonged expiratory time.
- PKC isoform expression varied with both postnatal age and brain region examined.
Conclusions:
- Endogenous PKC inhibition causes age-dependent reductions in ventilation, predominantly affecting respiratory timing mechanisms.
- The impact of PKC inhibition on ventilation decreases with advancing postnatal age.
- Immature respiratory systems appear more critically dependent on PKC activity for overall respiratory output compared to older animals.