David D. Kline, PhD

  • KLINE_David_2011Assistant Professor

Email: KlineDD@missouri.edu

Dalton Cardiovascular Research Center, Room 354

Teaching: Neural Control of the Circulation, Physiology

Neurohumoral Control of the Cardiovascular and Respiratory System.

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.

Kline DD. Chronic intermittent hypoxia affects integration of sensory input by neurons in the nucleus tractus solitarii. Respir Physiol Neurobiol. 2010 Apr 21. [Epub ahead of print] PubMed PMID: 20416405.

Kline DD, Ogier M, Kunze DL, Katz DM. Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J Neurosci. 2010 Apr 14;30(15):5303-10. PubMed PMID: 20392952.

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. 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. Epub 2009 Feb 25. PubMed PMID: 19244351; PubMed Central PMCID: PMC2681443.

Austgen JR, Fong AY, Foley CM, Mueller PJ, Kline DD, Heesch CM, Hasser EM. Expression of Group I metabotropic glutamate receptors on phenotypically different cells within the nucleus of the solitary tract in the rat. Neuroscience. 2009 Mar 17;159(2):701-16. Epub 2008 Oct 17. PubMed PMID: 19013221; PubMed Central PMCID: PMC2841035.

Wang Y, Garro M, Dantzler HA, Taylor JA, Kline DD, Kuehl-Kovarik MC. Age affects spontaneous activity and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons. Endocrinology. 2008 Oct;149(10):4938-47. Epub 2008 Jun 26. PubMed PMID: 18583421; PubMed Central PMCID: PMC2582911.

Kline DD. Plasticity in glutamatergic NTS neurotransmission. Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):105-11. 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.

Kline DD, Buniel MC, Glazebrook P, Peng YJ, Ramirez-Navarro A, Prabhakar NR, Kunze DL. Kv1.1 deletion augments the afferent hypoxic chemosensory pathway and respiration. J Neurosci. 2005 Mar 30;25(13):3389-99. PubMed PMID: 15800194.

Malik MT, Peng YJ, Kline DD, Adhikary G, Prabhakar NR. Impaired ventilatory acclimatization to hypoxia in mice lacking the immediate early gene fos B. Respir Physiol Neurobiol. 2005 Jan 15;145(1):23-31. PubMed PMID: 15652785.

Kline DD, Takacs KN, Ficker E, Kunze DL. Dopamine modulates synaptic transmission in the nucleus of the solitary tract. J Neurophysiol. 2002 Nov;88(5):2736-44. PubMed PMID: 12424308.

Prabhakar NR, Kline DD. Ventilatory changes during intermittent hypoxia: importance of pattern and duration. High Alt Med Biol. 2002 Summer;3(2):195-204. Review. PubMed PMID: 12162863.

Kline DD, Overholt JL, Prabhakar NR. Mutant mice deficient in NOS-1 exhibit attenuated long-term facilitation and short-term potentiation in breathing. J Physiol. 2002 Feb 15;539(Pt 1):309-15. PubMed PMID: 11850522; PubMed Central PMCID: PMC2290125.

Kline DD, Peng YJ, Manalo DJ, Semenza GL, Prabhakar NR. Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 alpha. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):821-6. Epub 2002 Jan 15. PubMed PMID: 11792862; PubMed Central PMCID: PMC117389.

Peng Y, Kline DD, Dick TE, Prabhakar NR. Chronic intermittent hypoxia enhances carotid body chemoreceptor response to low oxygen. Adv Exp Med Biol. 2001;499:33-8. PubMed PMID: 11729902.

Kline DD, Prabhakar NR. Role of nitric oxide in short-term potentiation and long-term facilitation: involvement of NO in breathing stability. Adv Exp Med Biol. 2001;499:215-9. PubMed PMID: 11729880.

Kline DD, Prabhakar NR. Peripheral chemosensitivity in mutant mice deficient in nitric oxide synthase. Adv Exp Med Biol. 2000;475:571-9. PubMed PMID: 10849697.

Ernsberger P, Koletsky RJ, Kline DD, Bedol DM, Friedman JE. The SHROB model of syndrome X: effects of excess dietary sucrose. Ann N Y Acad Sci. 1999 Nov 18;892:315-8. PubMed PMID: 10842673.

Kline DD, Yang T, Premkumar DR, Thomas AJ, Prabhakar NR. Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3. J Appl Physiol. 2000 Apr;88(4):1496-508. PubMed PMID: 10749847.

Kline DD, Yang T, Huang PL, Prabhakar NR. Altered respiratory responses to hypoxia in mutant mice deficient in neuronal nitric oxide synthase. J Physiol. 1998 Aug 15;511 ( Pt 1):273-87. PubMed PMID: 9679181; PubMed Central PMCID: PMC2231102.

Dalton Cardiovascular Research Center, Room 327-8
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