| dc.contributor.author | Gilbert, Robert William. | en_US |
| dc.date.accessioned | 2014-10-21T12:38:35Z | |
| dc.date.available | 1998 | |
| dc.date.issued | 1998 | en_US |
| dc.identifier.other | AAINQ36581 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55593 | |
| dc.description | Neuropeptides modulate the excitability of mammalian sympathetic neurons by their actions on various types of voltage- and ligand-gated ion channels. This thesis examines the actions of two neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) on dissociated adult guinea-pig and rat stellate ganglion (SG) neurons using whole-cell patch clamp recording methods. Voltage-gated ( K+ and Ca+2) and ligand-gated (nicotinic acetylcholine receptor, (nAChR)) conductances have been identified and characterized in these experiments. Under current-clamp conditions SG neurons exhibited overshooting action potentials (AP) followed by afterhyperpolarizations (AHP). The K+ channel blocker, tetraethylammonium (1 mM), the calcium channel blocker, Cd2+ (100--200 muM) and SP (500 nM) all depolarized SG neurons, reversibly decreased the AHP amplitude and increased the AP duration. In the presence of Cd2+, the effect of SP on membrane potential and AHP of guinea-pig SG neurons was reduced. Under voltage clamp, several different K+ currents were observed including: a transient outward K+ conductance, and a delayed rectifier outward K+ current (IK) consisting of Ca2+-sensitive IK(Ca), and Ca2+-insensitive components. Substance P (500 nM) inhibited the delayed rectifier outward K+ current. Pretreatment with Cd2+ (20--200 muM), or the high-voltage activated Ca2+ channel blocker o-conotoxin (10 muM), blocked SP's inhibitory effects on IK. This suggests that SP reduces the outward K+ current primarily through the inhibition of IK(Ca), and that this may occur, in part, via a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. Substance Ps actions on IK were mediated by a pertussis toxin-insensitive G protein coupled to NK1 tachykinin receptors. This mechanism did not appear to involve the actions of the cytosolic second messengers cyclic AMP, protein kinase A or C. A o-conotoxin-, Cd+2-sensitive inward Ba+2 current was also identified in guinea-pig SG neurons. Substance P (500 nM) and CGRP (500 nM) reduced inward Ba+2 current in guinea-pig SG neurons. Thus, the actions of SP on IK(Ca) may be due in part to a reduction in Ca2+ influx occurring via N-type Ca2+ channels. | en_US |
| dc.description | To determine a potential modulatory role of SP on ganglionic neurotransmission the actions of SP on nicotinic AChR ligand gated ionic current were investigated in rat SG neurons. In current-clamp, application of the nicotinic acetylcholine receptor agonist, DMPP (100 muM) depolarized the membrane potential by 30 mV. When neurons were voltage-clamped at a holding potential of --60 mV, DMPP activated an inward current which desensitized in the continued presence of the agonist. The DMPP-induced inward current was reduced by the nicotinic acetylcholine receptor antagonist mecamylamine (10 muM). The DMPP-inward current was reduced in Na+ -free ringers indicating that the current was carried primarily by Na+ ions. In the presence of 500 nM SP the amplitude of the DMPP induced current was reduced and the rate at which the current desensitized in the continued presence of DMPP was increased. | en_US |
| dc.description | This study presents the first description of ionic currents in mammalian SG neurons and demonstrates that SP and CGRP may modulate excitability in SG neurons via actions on voltage-gated and/or ligand-gated channels. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1998. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Molecular. | en_US |
| dc.subject | Biology, Neuroscience. | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.title | Actions of neuropeptides and neuroactive agents on membrane potential and ionic currents in cultured mammalian stellate ganglion neurons. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
