- Collection:
- Atlanta University and Clark Atlanta University Theses and Dissertations
- Title:
- Modulation of cardiac phsyiology in adult rat cardiomyocytes by protein kinase C and protein kinase, 2007
- Creator:
- Crawford, Brian H.
- Date of Original:
- 2007-02-01
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- theses
dissertations - Type:
- Text
- Format:
- application/pdf
- Description:
- This dissertation investigated the biochemical modifications and physiological changes associated with the phosphorylation of adult rat contractile proteins (Tnl and TnT) using protein kinase C (PKC) isozymes (a, 5, s, and Q and protein kinase A (PKA). It was hypothesized that the phosphorylation of adult rat cardiomyocytes by various PKC isozymes and PKA have specific substrates on myofibrils. It was also hypothesized that the phosphorylation of adult rat cardiomyocytes by PKC and PKA has alternating physiological effects on Mg 2+ ATPase activity, calcium sensitivity, and rate of myocyte contraction. Adult rat cardiomyofibrils were phosphorylated in vitro by PKC isozymes and PKA using [y-32P] ATP. PKC isozymes and PKA showed intermolecular specificities in phosphorylating rat cardiac myofibrils. These results were substantiated by the in situ phosphorylation of adult rat cardiomyocytes using 32P. Isolated cardiomyocytes were incubated with antagonists, agonist, inhibitors, or inducers of PKC isozymes and PKA adrenergic pathways. These treatments resulted in increased and decreased phosphorylation of myofibrillar substrates, consequently supporting the in vitro data that displayed substrate specificity of PKC and PKA. In general, phosphorylation of rat cardiac myofibrils by PKC isozymes (a, 5, e, and Q and PKA decreased myofibrillar Mg2+ATPase activity. However, they had diverse effects on calcium sensitivity. Phosphorylation of cardiomyocytes by PKC and PKA altered the velocity of contraction. The averages of the velocities were: control (untreated) -2.60 x 10"5 m/s, isoproterenol-6.00 x 10"5 m/s, phenylephrine- 3.47 x 10"5 m/s, TP A-1.67 x 10"5 m/s, and chlereythrine chloride-2.68 x 10"5 m/s. In summary, these results revealed that PKC isozymes and PKA phosphorylation of rat cardiomyofibrils have specific substrates, and alternative biochemical and physiological effects on cardiac muscle contraction.
Date of award: 12/1/2007
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: Department of Biological Sciences
Advisor: Jideama, Nathan M. - Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.td:2007_crawford_brian_h
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights:
-
