The long-term objective of this project is to understand the generation and transmission of mechanosensory information from the baroreceptor sensory terminal to its central termination in the nucleus of the solitary tract. This is part of a broader research effort to determine the neurophysiological and neuroanatomical substrate that underlies neural regulation of arterial pressure and cardiac rhythm. In this grant we are examining the distribution and the function of a new family of ion channels, the TRPC family of calcium permeable cation channels. These channels are important because they serve as a source of calcium influx that is expected to modulate the pattern of neuronal activity through effects on membrane potential, transmitter release at the central terminals and sensory discharge at the peripheral terminals. There are four specific aims: the first examines the distribution of the TRPC channels in the baroreceptor afferent fibers. Using immunohistochemistry, we will define the location of TRPC channels in the baroreceptor afferent pathway in three regions: the peripheral sensory receptors of myelinated and unmyelinated fibers in the arch of the aorta, in their soma in the nodose ganglion and in their synaptic terminals in the nucleus of the solitary tract. In the second aim we will ask what ligands activate these channels using an electrophysiological characterization of the channels in cell-attached patches and whole cell current in perforated patch whole cell recording. In the third aim we pursue the mechanism of activation by examining the effect of agonist on calcium influx using calcium imaging techniques to evaluate the contribution of the TRPC channels relative to the voltage-gated channels. Finally, in aim four we explore the functional consequence of activation of specific TRPC channels in whole cell voltage recording. These studies will include RNA interference to eliminate specific channels. ? ?
| 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 |
Showing the most recent 10 out of 11 publications
