Signaling Mechanisms to Physiological Function: Electrical and Second Messenger Communication in Resistance Arteries

Tran, Cam Ha T.

Signaling Mechanisms to Physiological Function: Electrical and Second Messenger Communication in Resistance Arteries

atmire.migration.oldid	141
dc.contributor.advisor	Welsh, Donald
dc.contributor.author	Tran, Cam Ha T.
dc.date.accessioned	2012-06-13T16:53:35Z
dc.date.available	2012-11-13T08:01:09Z
dc.date.issued	2012-06-13
dc.date.submitted	2012	en
dc.description.abstract	The goal of this thesis was to develop a deeper understanding of electrical and second messenger communication in small resistance arteries, and how these key biological processes influence vascular contractility and blood flow control. To achieve this goal, we pursued three defined objectives. First, we determined why electrical responses initiated in smooth muscle fail to spread to neighboring cells like their endothelial counterparts. A functional assessment complemented by computational modeling revealed that the structural and connectivity properties of vascular cells play a key role in determining how charge moves asymmetrically among vascular cells. As such, certain cell-specific responses will conduct robustly from cell-to-cell while others will not. Second, we examined the nature of electrical communication in arterial networks and how this key biological process impacts on blood flow control. Once again, using a combination of functional experimentation and computational modeling, we observed that vessel length and branching play a role in determining how electrical phenomenon conduct within a network and influence blood flow control. Further, this work re-emphasizes the essential role of the endothelium in electrical communication and how a modest change in this layer’s coupling, due to disease, can compromise network perfusion. Lastly, using an integrated experimental approach, we explored whether second messengers could cross myoendothelial gap junctions and elicit a feedback response that limits constriction. This pathway begins with agonists inducing smooth muscle cell depolarization and a rise in second messenger concentration. Next, IP3 fluxes across myoendothelial gap junctions and elicits inducible Ca2+ wavelets, an event that in turn activates endothelial IK channels. The resulting hyperpolarization then moderates iv the initial depolarization of smooth muscle. Overall, the findings arising from the three objectives shed new light onto the basis of vasomotor and blood flow control in the resistance vasculature.	en_US
dc.identifier.citation	Tran, C. H. (2012). Signaling Mechanisms to Physiological Function: Electrical and Second Messenger Communication in Resistance Arteries (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27781	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/27781
dc.identifier.uri	http://hdl.handle.net/11023/98
dc.language.iso	eng
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary	en
dc.publisher.place	Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Physiology
dc.subject.classification	Electrical Communication	en_US
dc.subject.classification	Second Messenger Communication	en_US
dc.subject.classification	Calcium Transients	en_US
dc.subject.classification	Myoendothelial Feedback	en_US
dc.subject.classification	Conducted Responses	en_US
dc.subject.classification	Ion Channels	en_US
dc.subject.classification	Gap Junctions	en_US
dc.subject.classification	Electrical Modeling	en_US
dc.subject.classification	Microcirculation	en_US
dc.subject.classification	Endothelial Cells	en_US
dc.subject.classification	Smooth Muscle Cells	en_US
dc.title	Signaling Mechanisms to Physiological Function: Electrical and Second Messenger Communication in Resistance Arteries
dc.type	doctoral thesis
thesis.degree.discipline	Cardiovascular & Respiratory Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.item.requestcopy	true