Ca 2+-Activated K+ Channels Limit the Chemosensitive Response of Locus Coeruleus (LC) Neurons
LC neurons are chemosensitive, increasing firing rate in response to hypercapnia through pH inhibition of K+ channels. This "accelerator" pathway is believed to set central respiratory gain. Using whole cell patch clamp, we found that hypercapnia activates L-type Ca2+ currents in LC neurons that increase early in life (from P1–P15) in rats. Using fluorescence imaging microscopy, we showed that these Ca2+ currents lead to a rise in cellular Ca2+. This increased Ca2+ could lead to activation of LC neuron KCa channels from P1–P15, resulting in neuronal hyperpolarization and a decreased magnitude of the firing rate response to hypercapnia with age. Consistent with this hypothesis, the KCa channel inhibitor paxilline enhanced the firing rate response of LC neurons to hypercapnia in an age-dependent manner. Further, the magnitude of the firing rate response of LC neurons to hypercapnia (determined as the Chemosensitivity Index) decreased with age from P1–P15 in parallel with the increase in the CO2-activated Ca2+channel activity. We are studying the development of Ca2+ and KCa channels in LC neurons using voltage clamp and immunohistochemical techniques. We propose a novel role for Ca2+ in LC neurons, activating a "brake" pathway that can lead to decreased central respiratory gain. Abnormalities of this pathway could result in breathing disorders. [NIH R01 HL56683, AHA Great Rivers Affiliate Predoctoral Fellowship].
Imber, A. N.,
Graham, C. D.,
& Putnam, R. W.
(2011). Ca 2+-Activated K+ Channels Limit the Chemosensitive Response of Locus Coeruleus (LC) Neurons. The FASEB Journal, 25 (Meeting Abstract Supplement).