Catecholaminergic neurons in the locus coeruleus (LC) play a role in the ventilatory response to hypercapnia. Here we show evidence for the involvement of TRP channels. We found that the input resistance was reduced during an exposure to 8% CO2 in ∼35% LC neurons in mouse brain slices, accompanied with depolarization and higher firing activity. The neuronal responses suggest the opening of Na+ or non-selective cationic channels instead of the closure of K+ channels. As a major group of cationic channels, the TRP channels are expressed in the brain, some of which are activated by acidic pH. We therefore screened all representative TRP channels using the quantitative real-time PCR analysis. High levels of mRNA expression of TRPC5, TRPM2 and TRPM7 were found in the LC tissue. Of them the TRPC5 transcript was the most abundant. The TRPC5 channel was activated by extracellular acidification when expressed in HEK cells. The TRPC5 currents started to be activated at pH 7.4 with pKa 6.9. The TRPC5 currents were also activated by isohydric hypercapnic and intracellular acidosis in a Ca2+-dependent manner. Consistently, the LC neurons were stimulated by both extra- and intracellular acidosis. The stimulatory effect of hypercapnia on LC neurons was eliminated by selective TRPC channel inhibitor SKF-96365 with and without the blockade of synaptic transmission. Single-cell PCR analysis indicated that TRPC5 mRNAs existed in the LC neurons. Thus these results strongly suggest that the TRP channels are likely to play a role in the CO2 chemosensitivity of LC neurons, especially the TRPC5.
- CO2 chemosensitivity
- Copyright © 2010, Journal of Neurophysiology