David D. Kline, PhD

Email: KlineDD@missouri.edu

Office:
573-884-0505
Dalton Cardiovascular Research Center, Room 354

Laboratory:
573-884-0426
Dalton Cardiovascular Research Center, Room 327-8

Teaching: Neural Control of the Circulation, Physiology

Research Interests:
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.

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

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

Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR. (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci USA. 100(17):10073-8.

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

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

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

Kline DD, Peng YJ, Manalo DJ, Semenza GL, Prabhakar NR. (2002) 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 USA. 99(2):821-6.

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

Kline DD, Yang T, Huang PL, Prabhakar NR. (1998) Altered respiratory responses to hypoxia in mutant mice deficient in neuronal nitric oxide synthase. J Physiol. 511:273-87.