David D. Kline, PhD
Professor, Department of Biomedical SciencesOffice Location: 354 DCRC
Office Phone: 573-884-0505
KlineDD@missouri.edu
Research Interests
Neurohumoral control of the cardiovascular and respiratory system
Research Description
Our laboratory focuses on the autonomic nervous system, in particular the cardiovascular and respiratory system. These vital systems operate to keep our bodies within 'normal' physiological limits to preserve homeostasis. When challenged acutely or chronically with low environmental oxygen levels (hypoxia) respiration, blood pressure and heart rate compensate to maintain arterial blood gas levels. This can happen during high altitude assent or disease states such as sleep apnea by activation of the chemoreceptor reflex. Additionally, arterial blood pressure is maintained during swings in pressure by the baroreceptor reflex. Both reflex pathways result from activation of neurons in the peripheral and central nervous system. Determining the mechanism of action of these reflex pathways during health and disease is the focus of the laboratory.
Several techniques are used to elucidate these mechanisms. These include 1) radiotelemetry in conscious animals to measure respiration, blood pressure or heart rate; 2) immunohistochemical localization of ion channels and neurotransmitter receptors to specific regions of the nervous system and individual neurons; 3) patch clamp techniques in isolated neurons for recording current flow through ion channels and 4) electrical recording of synaptic transmission in brainstem slices.
Using these techniques, we have recently discovered that chronic intermittent hypoxia, a model for obstructive sleep apnea, elicits a form of neural adaptation or plasticity in the brainstem. This includes changes in neurotransmitter release from presynaptic chemoreceptor afferent neurons as well as postsynaptic action potential firing. We are currently determining the mechanism of this altered neurotransmitter release.
Professional Background
- Obtained PhD, Case Western Reserve University.
- Obtained BA, Miami University.
Selected Publications
Matott MP, Kline DD. Activation of 5-hyrdoxytryptamine 7 receptors within the rat nucleus tractus solitarii modulates synaptic properties. Brain Res. 2016 Jan 15. pii: S0006-8993(16)00030-5. doi: 10.1016/j.brainres.2016.01.017. [Epub ahead of print] PubMed PMID: 26779891.
Matott MP, Ruyle BC, Hasser EM, Kline DD. Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function. J Neurophysiol. 2015 Dec 30:jn.01054.2015. doi: 10.1152/jn.01054.2015. [Epub ahead of print] PubMed PMID: 26719090.
Ostrowski TD, Ostrowski D, Hasser EM, Kline DD. Depressed GABA and glutamate synaptic signaling by 5-HT1A receptors in the nucleus tractus solitarii and their role in cardiorespiratory function. J Neurophysiol. 2014 Jun 15;111(12):2493-504. doi: 10.1152/jn.00764.2013. Epub 2014 Mar 26. PubMed PMID: 24671532; PubMed Central PMCID: PMC4044435.
Ostrowski TD, Hasser EM, Heesch CM, Kline DD. H₂O₂ induces delayed hyperexcitability in nucleus tractus solitarii neurons. Neuroscience. 2014 Mar 14;262:53-69. doi: 10.1016/j.neuroscience.2013.12.055. Epub 2014 Jan 4. PubMed PMID: 24397952; PubMed Central PMCID: PMC4523391.
Kline DD. Chronic intermittent hypoxia affects integration of sensory input by neurons in the nucleus tractus solitarii. Respir Physiol Neurobiol. 2010 Nov 30;174(1-2):29-36. doi: 10.1016/j.resp.2010.04.015. Epub 2010 Apr 21. PubMed PMID: 20416405; PubMed Central PMCID: PMC2953573.
Kline DD, King TL, Austgen JR, Heesch CM, Hasser EM. Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius neurons that project to the rostral ventrolateral medulla. Neuroscience. 2010 May 5;167(2):510-27. doi: 10.1016/j.neuroscience.2010.02.012. Epub 2010 Feb 12. PubMed PMID: 20153814; PubMed Central PMCID: PMC2849863.
Kline DD, Hendricks G, Hermann G, Rogers RC, Kunze DL. Dopamine inhibits N-type channels in visceral afferents to reduce synaptic transmitter release under normoxic and chronic intermittent hypoxic conditions. J Neurophysiol. 2009 May;101(5):2270-8. doi: 10.1152/jn.91304.2008. Epub 2009 Feb 25. PubMed PMID: 19244351; PubMed Central PMCID: PMC2681443.
Kline DD. Plasticity in glutamatergic NTS neurotransmission. Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):105-11. doi: 10.1016/j.resp.2008.04.013. Review. PubMed PMID: 18524694; PubMed Central PMCID: PMC2666915.
Kline DD, Ramirez-Navarro A, Kunze DL. Adaptive depression in synaptic transmission in the nucleus of the solitary tract after in vivo chronic intermittent hypoxia: evidence for homeostatic plasticity. J Neurosci. 2007 Apr 25;27(17):4663-73. PubMed PMID: 17460079.
