Central chemoreception, the mechanism by which the brain senses CO2/pH and regulates breathing, is thought to involve neurons on the ventral surface of the medulla oblongata within the retrotrapezoid nucleus (RTN). However, the cellular identity and molecular mechanism of these RTN chemoreceptors is unknown. Recently we identified a population of CO2-sensitive RTN that may be the elusive RTN chemoreceptors; i.e., extensive superficial dendrites, are glutamatergic and project directly to respiratory centers. In the brain slice, RTN neurons with a similar morphology are intrinsically pH-sensitive and express an open rectifying pH-sensitive K+ current that is active at resting membrane potential, thus suggesting that a pH-sensitive background K+ (e.g., TASK) contributes to intrinsic pH sensitivity of RTN neurons. In this research proposal I use electrophysiological techniques to determine if a TASK-like current is expressed by pH sensitive RTN neurons (Specific Aim 1) and single cell RT-PCR to determine if TASK mRNA transcripts are made by RTN neurons (Specific Aim 2). Results from these experiments will determine if TASK currents are present in pH-sensitive RTN neurons and provide insight into the cellular mechanism of mechanism chemoreception. ? ?
| Kréneisz, Orsolya; Benoit, Justin P; Bayliss, Douglas A et al. (2009) AMP-activated protein kinase inhibits TREK channels. J Physiol 587:5819-30 |
| Mulkey, Daniel K; Talley, Edmund M; Stornetta, Ruth L et al. (2007) TASK channels determine pH sensitivity in select respiratory neurons but do not contribute to central respiratory chemosensitivity. J Neurosci 27:14049-58 |
| Mulkey, Daniel K; Rosin, Diane L; West, Gavin et al. (2007) Serotonergic neurons activate chemosensitive retrotrapezoid nucleus neurons by a pH-independent mechanism. J Neurosci 27:14128-38 |
| Mulkey, Daniel K; Mistry, Akshitkumar M; Guyenet, Patrice G et al. (2006) Purinergic P2 receptors modulate excitability but do not mediate pH sensitivity of RTN respiratory chemoreceptors. J Neurosci 26:7230-3 |
