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Type of Document Thesis Author Yang, Kai Author's Email Address kai@bio.fsu.edu URN etd-05062004-115043 Title The Initiating Mechanism of Premature Trypsin Activation in Pancreatitis Degree Master of Science Department Biological Science, Department of Advisory Committee
Advisor Name Title George Bates Committee Co-Chair Wei-Chun Chin Committee Co-Chair Laura Keller Committee Member Thomas Keller Committee Member Keywords
- Acute Pancreatitis
- Matrix
- Ion Exchange
- Zymogen Granule
Date of Defense 2004-03-21 Availability unrestricted Abstract Under normal physiological conditions, trypsin remains inactive as trypsinogen inside the pancreas. Upon entering the small intestine, trypsinogen is converted to active trypsin. Acute pancreatitis is caused by premature activation of trypsinogen and the digestion of the pancreas. Up to now the exact initiating mechanism of this premature activation is still not clear. In these experiments, pH fluctuations, Ca2+ concentration changes and trypsin activity inside pancreatic zymogen granules were monitored. The effects of possible pharmacological inhibitors were also assessed. The results show that a sustained increase of Ca2+ in the cytosol can trigger K+ influx into zymogen granules (ZGs) via a Ca2+-activated K+ channel (ASKCa). This influx of K+ then mobilizes bound Ca2+ by Ca2+/K+ ion-exchange to increase free Ca2+ concentration in the ZGs and also mobilizes bound H+ by H+/K+ ion-exchange to decrease the pH in the ZGs. Both the increase of free Ca2+ concentration and the decrease of pH in the ZGs will facilitate trypsinogen autoactivation and stabilize active trypsin. Moreover these investigations show that the ASKCa in the membrane of ZGs may be a small conductance Ca2+-activated K+ channel (SKCa channel), because it can be activated by 300 nM [Ca2+] and inactivated by apamin (100 nM) and TEA (20 mM).Files
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