Queen's University - Utility Bar

QSpace at Queen's University >
Theses, Dissertations & Graduate Projects >
Queen's Theses & Dissertations >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1974/1004

Title: Neural Regulation in Circular Smooth Muscle of Mouse Lower Esophageal Sphincter
Authors: Zhang, Yong

Files in This Item:

File Description SizeFormat
Zhang_Yong_200801_PhD.pdf24.66 MBAdobe PDFView/Open
Keywords: Murine
Neurotransmitter
Smooth Muscle
Interstitial Cells of Cajal
Neurotransmission
Chloride Channels
Issue Date: 2008
Series/Report no.: Canadian theses
Abstract: The lower esophageal sphincter (LES) is characterized by basal tone and appropriately timed neurogenic relaxation. The physiological mechanisms underlying these crucial LES functions remain poorly understood. The current studies were designed to characterize the electrophysiological properties and neural regulation of LES circular smooth muscle (CSM), and to determine whether interstitial cells of Cajal (ICC) play a role in neurotransmission. Conventional intracellular recordings were performed in CD1, nNOS knock-out, eNOS knock-out and W/Wv mutant mice. Mouse LES consists of “sling” and “clasp” smooth muscle, which were studied separately in CD1 mice. In subsequent studies of mutant mice and respective controls, only the clasp muscle was examined, Immunohistochemical c-Kit staining of ICC was performed in wild-type and W/Wv mutant mice that were first characterized electrophysiologically. The smooth muscle of the LES clasp and sling displayed unitary membrane potentials with a resting membrane potential (RMP) of ~ -43 mV. Spontaneous nifedipine-sensitive action potentials superimposed on the unitary potentials were usually recorded in the LES clasp, but not sling muscle. A monophasic inhibitory junction potential (IJP) was recorded in sling CSM, whereas a biphasic IJP consisting of an initial IJP, followed by long-lasting slow IJP (LSIJP) was recorded in clasp. Further pharmacological studies using control and various knockout mice suggest that: 1. the CSM of the mouse LES is innervated by cholinergic, nitrergic and purinergic nerves; 2. the LSIJP is mediated entirely by nitrergic nerves, whereas purinergic and nitrergic nerves produce the monophasic IJP in the LES sling and initial phase of biphasic IJP in the LES clasp; 3. Ca2+/CaM-kinase II is involved in the regulation of the nitrergic IJPs; 4. TREK-1 K+ channels are not involved in the nitrergic IJP; 5. purinergic and cholinergic neurotransmission is intact in LES CSM of W/Wv mutant mice, whereas nitrergic neurotransmission is impaired in about half of the animals. In animals in which nitrergic neurotransmission was intact, ICC-IM were markedly deficient immunohistologically, suggesting that ICC are not required for nitrergic neurotransmission; 6. impaired nitrergic neurotransmission in W/Wv mutant mice is associated with dysfunction of a Ca2+-dependent signaling cascade primed by spontaneous Ca2+ release from the sarcoplasmic reticulum.
Description: Thesis (Ph.D, Physiology) -- Queen's University, 2008-01-24 15:54:52.175
URI: http://hdl.handle.net/1974/1004
Appears in Collections:Physiology Graduate Theses
Queen's Theses & Dissertations

Items in QSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  DSpace Software Copyright © 2002-2008  The DSpace Foundation - TOP