The arterial baroreceptor (BR) reflex plays an essential role in autonomic control of the heart. Altered discharge of BR afferents occurs with hypertension and heart failure and is therefore inextricably linked to autonomic nervous system dysfunction. BR are broadly classified as myelinated or unmyelinated afferents, each exhibiting distinct discharge patterns in response to arterial pressure changes. The micromechanical environment of the peripheral termination certainly plays a role in the process of pressure transduction. However, the operational differences in sensory coding between these two functional phenotypes may also arise from unique distributions of ion channels at critical points along the afferent pathway (e.g. arterial pressoreceptor, cell body, central synapse). Unfortunately, such a bimodal demarcation belies the continuum of physiological properties exhibited by BR and makes difficult the integration of cellular and systems level observations. For example, selective recruitment of myelinated or unmyelinated BR via electrical excitation of voltage-gated ion channels (i.e. activation independent of mechanotransduction) evokes dramatically different heart rate and blood pressure reflex responses. The ionic mechanisms that contribute to the differential sensory encoding properties of myelinated and unmyelinated BR are largely unknown. Here, we use a newly developed adult rat nerve-ganglion preparation for patch clamp study of fluorescently identified aortic baroreceptor neurons which ensures unambiguous classification of sensory modality and afferent fiber type. Preliminary data are suggestive of a differential utilization of voltage- and ligand-gated ion channels that may potentially explain some of the contrasting pressure encoding properties of myelinated and unmyelinated BR. For example, neural discharge from myelinated afferents appears less dependent upon N-type Ca2+. (ICa,N)and BK-type Ca2+-activated K+ (IKCa,BK)ion channels than activity arising from unmyelinated afferents, despite voltage clamp evidence for functional coexpression of ICa,N and IKCa,BK in both phenotypes. Such differential ionic mechanisms may underlie the disparate neural encoding properties of myelinated and unmyelinated BR and could potentially influence brainstem integration of cardiovascular afferent information if similarly represented at the presynaptic terminals. These fundamental details may lead to novel pharmacological strategies in the management of cardiovascular pathologies such as acute hypertension and dysrhythmias that are well known to involve or invoke autonomic reflexes through BR activation. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072012-04
Application #
7080394
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Barouch, Winifred
Project Start
2003-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$330,668
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Santa Cruz Chavez, Grace C; Li, Bai-Yan; Glazebrook, Patricia A et al. (2014) An afferent explanation for sexual dimorphism in the aortic baroreflex of rat. Am J Physiol Heart Circ Physiol 307:H910-21
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Li, Bai-Yan; Glazebrook, Patricia; Kunze, Diana L et al. (2011) KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents. Am J Physiol Cell Physiol 300:C1393-403
Maruyama, Mitsunori; Li, Bai-Yan; Chen, Hanying et al. (2011) FKBP12 is a critical regulator of the heart rhythm and the cardiac voltage-gated sodium current in mice. Circ Res 108:1042-52
Zhou, Yu-Hong; Sun, Li-Hua; Liu, Zhen-Hong et al. (2010) Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat. Clin Exp Pharmacol Physiol 37:852-61
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Qiao, Guo-Fen; Li, Bai-Yan; Lu, Yan-Jie et al. (2009) 17Beta-estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats. Am J Physiol Cell Physiol 297:C654-64
Li, Bai-Yan; Qiao, Guo-Fen; Feng, Bin et al. (2008) Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat. Am J Physiol Regul Integr Comp Physiol 295:R1301-10
Wladyka, Cynthia L; Feng, Bin; Glazebrook, Patricia A et al. (2008) The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats. J Physiol 586:795-802
Li, Bai-Yan; Schild, John H (2007) Electrophysiological and pharmacological validation of vagal afferent fiber type of neurons enzymatically isolated from rat nodose ganglia. J Neurosci Methods 164:75-85

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