We are studying the expression of voltage-gated ion channels in the soma and terminals of baroreceptor neurons whose mechanosensitive terminals lie in the adventitia of walls of major arteries. We have proposed that these channels underlie the markedly different firing patterns of the receptors connected to unmyelinated versus myelinated fibers as they respond to changes in arterial pressure. In particular, this proposal focuses on the identification, followed by functional assessment, of the specific voltage-gated potassium channels. These channels shape the action potential and discharge patterns and they are frequent targets of neuromodulators. In the first aim we will determine which of the members of the potassium channel families, Kvl, Kv2, Kv3 and Kv4, are present in the soma of baroreceptor neurons through the use of RT-PCR, in situ hybridization and channel specific antibodies.
In aim two we will move to the peripheral terminal, the actual baroreceptor, to ask whether the channels that are present in the soma are also present on the peripheral terminals. We will use immunocytochemical techniques to explore the distribution of the ion channels within the terminals of both myelinated and unmyelinated fibers using confocal microscopy.
In Aim 3 we will examine the functional role of the specific potassium channels. To do this we are using anti-sense strategy in identified baroreceptor neurons. The contributions of a distinct channel to resting membrane potential, action potential and to the discharge produced by depolarization will be examined. Finally, in Aim 4 we will tie together the electrophysiological characterization with anatomical localization of the channels identified in AIMS 1-3 in mathematical models that allow us to make testable predictions for the role of each of these channels A and C baroreceptor neurons.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL061436-05
Application #
6625282
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Lathrop, David A
Project Start
1998-12-01
Project End
2003-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
5
Fiscal Year
2003
Total Cost
$229,755
Indirect Cost
Name
Case Western Reserve University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Moore, Brian M; Jerry Jou, Chuanchau; Tatalovic, Milos et al. (2014) The Kv1.1 null mouse, a model of sudden unexpected death in epilepsy (SUDEP). Epilepsia 55:1808-16
Schild, John H; Kunze, Diana L (2012) Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents. Auton Neurosci 172:4-12
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
Ramirez-Navarro, Angelina; Glazebrook, Patricia A; Kane-Sutton, Michelle et al. (2011) Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract. J Neurophysiol 105:2772-80
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
Wladyka, Cynthia L; Kunze, Diana L (2006) KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons. J Physiol 575:175-89
Glazebrook, Patricia A; Schilling, William P; Kunze, Diana L (2005) TRPC channels as signal transducers. Pflugers Arch 451:125-30
Kline, David D; Buniel, Maria C F; Glazebrook, Patricia et al. (2005) Kv1.1 deletion augments the afferent hypoxic chemosensory pathway and respiration. J Neurosci 25:3389-99
Doan, Thanh N; Stephans, Kevin; Ramirez, Angelina N et al. (2004) Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers. J Neurosci 24:3335-43
Ramirez, Angelina N; Kunze, Diana L (2002) P2X purinergic receptor channel expression and function in bovine aortic endothelium. Am J Physiol Heart Circ Physiol 282:H2106-16

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