Cardiac performance, angiogenesis and growth was investigated during early chicken development. Heart rate, and thus arterial pulse pressure and cardiac output, were altered with the bradycardic drug ZD7288. Heart rates at 72 h of development of control embryos and those dosed with chicken Ringer were not different at 171 bpm. Acute and chronic application of ZD7288 caused significant bradycardia. Chronic dosing of Ringer and ZD7288 changed neither eye diameter nor development rate. Chronic dosing of ZD7288 did not significantly alter CAM vessel density close to the embryo (2, 3 and 4 mm) but at farther distances (5 and 6 mm) chronic dosing with both Ringer and ZD7288 decreased vessel density by 13 - 16%. Chronic dosing with ZD7288 also reduced body mass by 20%. Thus, lowered heart rate and cardiac output had little effect on vessel density or developmental stage, but did reduce embryo growth.

It is well established that the septo-hippocampal system is involved in memory. The medial septum is connected to the hippocampus via the fimbria fornix, which consists mostly of acetylcholine and ã-aminobutyric acid (GABA) projection neurons. The contributions of the cholinergic projection to memory have been studied extensively; whereas, the role of the GABAergic projection is not well characterized. The present experiment tested whether septal infusions of the selective H-channel blocker ZD7288 would impair spontaneous alternation (SA) and continuous multiple inhibitory avoidance (CMIA). Fifteen minutes prior to assessing SA or CMIA, different groups of male Sprague-Dawley rats were given septal infusions of saline or ZD7288 (0.2, 0.6 or 1.5 nmol / 0.5ìl). Our results indicate that septal infusions of ZD7288 impaired SA in a dose-dependent manner; the same infusions did not affect CMIA. This is the first demonstration that H-channels on septo-hippocampal GABAergic projection neurons are involved in memory.

Neurons perform complex computations, communications and precise transmissions of information in the form of action potentials (APs). The high level of heterogeneity and complexity at all levels of organization within a neuron and the functional requirement of highly permeable cell membranes leave neurons exposed to damage when energy levels are insufficient for the active maintenance of ionic gradients. When energy is limiting the ionic gradient across a neuron’s cell membrane risks being dissipated which can have dire consequences. Other researchers have advocated “generalized channel arrest” and/or “spike arrest” as a means of reducing the neuronal permeability allowing neurons to adjust the demands placed on their electrogenic pumps to lower levels of energy supply. I investigated the consequences of hypoxia on the propagation of a train of APs down the length of a fast conducting axon capable of transmitting APs at very high frequencies. Under normoxic conditions I found that APs show conduction velocities and instantaneous frequencies nearly double that of neurons experiencing energy limiting hypoxic conditions. I show that hypoxia affects AP conduction differently for different lengths of axon and for APs of different instantaneous frequencies. Action potentials of high instantaneous frequency in branching lengths of axon within ganglia were delayed more significantly than those in non-branching lengths contained within the connective and fail preferentially in branching axon. I found that octopamine attenuates the effects of hypoxia on AP propagation for the branching length of axon but has no effect on the non-branching length of axon. Additionally, for energetically stable cells, application of the anti-diabetic medication metformin or the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 resulted in a reduced performance similar to that seen in neurons experiencing energetic stress. Furthermore both metformin and ZD7288 affect the shape of individual APs within an AP train as well as the original temporal sequence of the AP train, which encodes behaviourally relevant information. I propose that the reduced performance observed in an energetically compromised cell represents an adaptive mechanism employed by neurons in order to maintain the integrity of their highly heterogeneous and complex organization during periods of reduced energy supply. / Thesis (Master, Biology) -- Queen's University, 2011-10-07 14:41:46.972