Protein kinase C modulates ventilatory patterning in the developing rat

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/k g, intraperitoneally). Ro 32-0432 decreased minute ventilation ((V) over do t E) by 51.0 +/- 5.5% (mean +/- SEM) in youngest pups (p < 0.01) but only 1 9.1 +/- 6.8% in 20-21-d-old pups (p < 0.01). (V) over dot E decreases were always due to frequency reductions with tidal volume (VT) remaining unaffec ted, Respiratory rate decreases primarily resulted from marked expiratory t ime (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, a nd mu was further examined in brainstem and cortex by immunoblotting and re vealed different patterns with postnatal age and location. We conclude that endogenous PKC inhibition elicits age-dependent ventilatory reductions whi ch 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.