RODNEY L. PARSONS
Professor and Chair
Anatomy and Neurobiology
Ph.D., Stanford University, 1965
Cardiovascular disease is a major cause of death in the USA and dysfunction of the neural regulation of the heart is an important factor in the etiology of cardiac disease. An emphasis of current research activities is the elucidation of mechanisms that regulate the excitability of parasympathetic cardiac and sympathetic neurons innervating cardiac tissues.
One question under investigation analyzes mechanisms that underlie synaptic integration and excitability of neurons within the intrinsic cardiac ganglia. Historically, the parasympathetic cardiac ganglia were considered relay stations: sites simply transmitting preganglionic information with minimal modification to the postganglionic cells innervating cardiac tissue. We now know that afferent fibers and sympathetic postganglionic axons, in addition to parasympathetic preganglionic fibers, innervate the cardiac ganglia. Each of these neural inputs utilizes different chemical neurotransmitters. Ongoing studies test the hypothesis that the collective cardiac ganglia form an Intrinisic Cardiac Nervous System (ICNS), which receives multiple neurochemical signals that are capable of modulating the inhibitory output of the cardiac neurons to the heart. Recent studies have shown that exogenous or neurally-released pituitary adenylate cyclase-activating polypeptide (PACAP) depolarizes and increases membrane excitability of the cardiac neurons. We are determining the underlying ionic mechanisms and intracellular signaling cascades responsible for PACAP’s actions. These experiments use whole cell patch clamp recording techniques on dissociated neurons and intracellular recordings from neurons in intact whole mount ganglia preparations to determine second messenger-induced modulation of ion channel function. In addition, high speed, confocal imaging techniques analyze transmitter-induced alterations in intracellular calcium.
A second area of interest is the response of the cardiac neurons to injury. Cardiac neurons can be axotomized during transplantation or injured during laser surgery to ablate ectopic pacemaker sites. However, the cardiac ganglia are not readily accessible for in vivo studies. Thus, we have developed an explant-cultured guinea pig ICNS preparation in which concentrations of parasympathetic preganglionic fiber-derived regulatory factors such as PACAP and cardiac tissue-derived regulatory factors such as neurturin are minimal. This preparation allows us to analyze, using electrophysiological, immunocytochemical and PCR techniques, the role of PACAP and neurturin in the regulation of the electrical and chemical phenotype of the cardiac neurons. The studies of the modulation of electrical properties and chemical phenotype of neurons within the ICNS should elucidate how alterations in the neural input or response following injury might contribute to the initiation of cardiac arrhythmias.A third question concerns the mechanisms underlying somatic release of quantal ATP from dissociated guinea pig sympathetic stellate neurons. Somatic transmitter release may be a key mechanism by which neurons signal within peripheral ganglia, including the sensory dorsal root ganglia and autonomic ganglia. Our earlier studies showed that somatic vesicular ATP was released in a voltage- and calcium-dependent mechanism and that the released ATP activated P2X receptors expressed on the same neurons. The ongoing studies analyze the role of calcium-induced calcium release and calcium sequestration by mitochondria in the regulation of somatic ATP release. These studies use a combination of current clamp and voltage clamp recording from dissociated neurons.
Merriam, L.A., Locknar, S,A,, Girard, B.M. and Parsons R.L. Somatic ATP release from guinea pig sympathetic neurons does not require calcium-induced calcium release from internal stores. Am J Physiol Cell Physiol. 299:836-843, 2010.
Tompkins J.D., Y.T. Lawrence and R.L. Parsons. Enhancement of Ih, but not an inhibition of IM, is a key mechanism underlying the PACAP-induced increase in excitability of guinea pig intrinsic cardiac neurons. Am J Physiol Regul Integr and Comp Physiol. 297:52-59, 2009.
Young, B.A., Girard, B.M. and Parsons, R.L. Neurturin suppresses injury-induced neuronal activating transcription factor 3 expression in cultured guinea pig cardiac ganglia. J. Comp. Neurol. 508:795-805, 2008.
Girard, B.M., B.A. Young, T.R. Buttolph, S.L. White and R.L. Parsons. Regulation of neuronal pituitary adenylate cyclase-activating polypeptide (PACAP) expression during culture of guinea pig cardiac ganglia. Neuroscience 146: 584-593, 2007.
Tompkins, J.D., Ardell, J.L., Hoover, D.B. and R.L. Parsons. Neurally-released pituitary adenylate cyclase-activating polypeptide enhances guinea pig intrinsic cardiac neurone excitability. J. Physiol. 582.1: 87-93, 2007.
Girard, B.M., B.A. Young, T.R. Buttolph, S.A. Locknar, S.L. White and R.L. Parsons. Trophic factor modulation of cocaine- and amphetamine-regulated transcript peptide expression in explant cultured guinea-pig cardiac neurons. Neuroscience. 139: 1329-1341, 2006.
Parsons, R.L., S.A. Locknar, B. A. Young, J. L. Hoard, and D. B. Hoover. Presence and co-localization of vasoactive intestinal polypeptide (VIP) with neuronal nitric oxide synthase (nNOS) in cells and nerve fibers within guinea pig intrinsic cardiac ganglia and cardiac tissue. Cell & Tiss Res. 323(2):197-209, 2006.
Tompkins, J.D., J.C. Hardwick, S.A. Locknar, L.A. Merriam and R.L. Parsons. Ca2+ influx, but not Ca2+ release from internal stores, is required for the PACAP-induced increase in excitability in guinea pig intracardiac neurons. J Neurophysiol. 95(4):2134-42, 2006.
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Last modified July 19 2012 09:18 AM