First Advisor

Keith D. Garlid

Term of Graduation

Fall 2008

Date of Publication


Document Type


Degree Name

Doctor of Philosophy (Ph.D.) in Biology






Cellular signal transduction, Cardiotonic agents, Heart cells, Mitochondria



Physical Description

1 online resource (2, xi, 201 pages)


Intracellular responses to external stimuli require reception of the message at the plasma membrane followed by encoding and transmission of the message to its effectors downstream. In this process, diverse cellular responses are mediated by many redundant molecular players. The apparent generality and redundancy of many kinases, such as the mitogen-activated protein kinases (MAPKs), suggests that signal transduction must gain specificity through tight regulation. Diffusion and random collisions of relevant signaling components seem insufficient to explain the multilayered complexity observed in cell signaling cascades. Emerging hypotheses suggest that signaling machinery may achieve enhanced specificity and control by exploiting the compartmentalization capabilities of plasma membrane microdomains. This study examines the hypothesis that treatment of the heart with the cardioprotective agents, ouabain or bradykinin, instigates formation of a signaling platform (or signalosome) that encompasses all the enzymes of the receptor-mediated pathway. The signalosome serves to compartmentalize and deliver the signaling components to mitochondria where it facilitates opening of the mitochondrial ATP-sensitive K+ channel and instigation of an intramitochondrial signaling pathway that mediates cardioprotection.


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