John H. Schild, Ph.D.
Associate Professor, Biomedical Engineering Program
Adjunct Assistant Professor, Department of Biology
Ph.D. Bioengineering, Rice University (1994)
Cellular Electrophysiology/Computational Neuroscience.
More than 83 million Americans have some form of cardiovascular disease (CVD). The mortality rate for CVD recently surpassed 800,000 deaths per year, impacting about the same number of males as females (49% and 51%, American Heart Association, Executive Summary 2013.) The clinical manifestations of CVD are well described but comparatively little is known regarding the neural mechanisms underlying the control of the heart and circulation. For example, the autonomic nervous system (ANS) is critically important to cardiovascular homeostasis but the extent to which the ANS impacts the etiology and progression of CVD is poorly understood. Fundamental to the operation of the ANS are ion channels, which are membrane bound proteins that give rise to the bioelectrical properties of the human nervous system. Ion channels and similar membrane bound proteins as well numerous subcellular modulatory pathways are frequent targets for many of the pharmacological interventions used by cardiologists. Our lab seeks to better understand how these medicines impact the many neurosensory reflexes involved in the ANS control of cardiovascular function. Of these, the baroreceptor reflex (BRX) is widely recognized as the dominant pathway impacting beat-to-beat control of heart rate and blood pressure.
Baroreceptors (BR) are pressure sensitive nerve endings that relay information to the brain concerning the magnitude and rate of change of arterial pressure. Many of our clinically relevant questions and laboratory experiments are centered around BR function. Our laboratory utilizes a synergistic combination of: 1) in vitro patch clamp for electrophysiological study of fluorescently identified BR sensory neurons both in isolation and within an intact vagal ganglion preparation where the afferent type can be reliably identified through measure of fiber conduction velocity, 2) in vitro patch clamp for electrophysiological study of fluorescently identified 2nd order BR neurons and neural circuits in the nucleus of the solitary tract (NTS) using thin slices of brainstem tissue, 3) an in vitro aortic arch preparation for quantifying the pressure-dependent discharge from single BR nerve fibers, and 4) an in situ whole animal preparation for integrated study of the parasympathetic limb of the BRX. Our team was the first to identify a gender-related bias in aortic BR fiber type, the neural encoding of arterial pressure and the neurocirculatory dynamics of the BRX. Morphometric analyses of aortic BR fibers and electrophysiological study of BR neurons from an animal model (rat) has shown that females have about 50% more myelinated BR, providing a functionally distinct subtype of low threshold myelinated BR rarely present in age-matched males (< 2%). We have also shown that physiological levels of estradiol, a potent, naturally occurring estrogenic hormone can activate a G protein coupled receptor (GPR30) capable of modulating the excitability of this gender specific subtype of BR afferent. Further study of the gender-related differences in the neural integration of BR sensory information from the pressure sensitive BR terminal through to 2nd-order BR neurons in the NTS could potentially lead to novel advances in the management of cardiovascular health and disease which is widely noted to be sexually dimorphic. Our efforts have been funded through grants from the American Heart Association and more recently the National Heart, Lung and Blood Institute of the NIH (HL081819 and HL072012).
Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents. Schild JH, Kunze DL. Auton Neurosci. 2012 Dec 24;172(1-2):4-12.
KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents. Li BY, Glazebrook P, Kunze DL, Schild JH. Am J Physiol Cell Physiol. 2011 Jun;300(6):C1393-403
17Beta-estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats. Qiao GF, Li BY, Lu YJ, Fu YL, Schild JH. Am J Physiol Cell Physiol. 2009 Sep;297(3):C654-64
Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat. Li BY, Qiao GF, Feng B, Zhao RB, Lu YJ, Schild JH. Am J Physiol Regul Integr Comp Physiol. 2008 Oct;295(4):R1301-10
The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats.
Wladyka CL, Feng B, Glazebrook PA, Schild JH, Kunze DL. J Physiol. 2008 Feb 1;586(3):795-802
Theoretical and electrophysiological evidence for axial loading about aortic baroreceptor nerve terminals in rats. Feng B, Li BY, Nauman EA, Schild JH. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3659-72
Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge. Schild JH, Kunze DL. J Neurophysiol. 1997 Dec;78(6):3198-209
A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. Schild JH, Clark JW, Hay M, Mendelowitz D, Andresen MC, Kunze DL. J Neurophysiol. 1994 Jun;71(6):2338-58.