The Ca2+‐activated K+ channels play a braking role in locus coeruleus neurons during CO2 exposure (872.1)

Abstract

The LC has an important role in central chemoreception and K+ channels have been suggested to be sensitive to changes of pH. Studies have shown that some ion channels present in the cell membrane of LC neurons, among them the Ca2+‐activated K+ channels (KCa), are activated by high levels of CO2. These channels appear to hyperpolarize LC neurons and limit increased firing rate in response to hypercapnic acidosis. We evaluated the participation of KCa in the CO2‐drive to breath in unanesthetized adult rats by bilaterally microinjecting Paxiline (KCa blocker, 100µM or 500µM / 0.1µL) or vehicle (aCSF) intra‐LC. Bilateral KCa blockade in LC neurons did not affect resting ventilation. However, the increase in ventilation produced by hypercapnia (7% CO2) was amplified by 39 and 33% after Paxilline (100µM or 500µM, respectively) injection (1305.2 ± 164.2 mL.kg‐1.min‐1 in vehicle group vs 1822.0 ± 201.7 in Paxilline 100µM group and 1735.3 ± 116.5 in Paxilline 500µM group) due largely to a increase in tidal volume. The results suggest that KCa++ modulate the hypercapnic ventilatory response as braking pathway, but that they are not involved in respiratory control during normocapnia, in the LC of adult rats.Grant Funding Source: FAPESP and CNPq