Gap Junction Blockade in the Locus Coeruleus (LC) Decreases the Hypercapnic Ventilatory Response
The LC has an important role in central chemoreception and its contribution decreases with development. In neurons from young rats (P9 or younger), the % of LC neurons that increase firing rate in response to hypercapnia is 85% while it is only about 45% in neurons from rats P10 or older. Carbenoxolone (CARB - gap junction blocker) has very little effect on this response in neurons from the youngest rats, with the % responding dropping only to 70% in the presence of CARB. However, CARB decreases the % responding by half in older animals, dropping it to 21%. We evaluated the participation of gap junctions in the CO2ventilatory response in conscious adult rats by bilaterally microinjecting CARB (1mM or 3mM / 0.1 μL) or vehicle (artificial cerebrospinal fluid) into the LC of Wistar rats. Bilateral gap junction blockade in LC neurons did not affect resting ventilation. However, the increase in ventilation produced by hypercapnia (7% CO2) was reduced by 20% after CARB injection (1904.5 ± 95.2 in vehicle group vs 1518.0 ± 76.1 mL/kg/min in CARB 3mM group and 1468.3 ± 122.2 mL/kg/min in CARB 1mM) due largely to a decrease in respiratory frequency. The results suggest that gap junctions modulate the hypercapnic ventilatory response, but that they are not involved in respiratory control during normocapnia, in the LC of rats older than P10.
Financial support: INCT-Fisiologia Comparada, FAPESP, CNPq, and NIH Grant HL56683.
Patrone, L. G.,
Bicego, K. C.,
Hartzler, L. K.,
Putnam, R. W.,
& Gargaglioni, L. H.
(2012). Gap Junction Blockade in the Locus Coeruleus (LC) Decreases the Hypercapnic Ventilatory Response. The FASEB Journal, 26 (Meeting Abstract Supplement).