K+-induced ion-exchanges trigger trypsin activation in pancreas acinar zymogen granules.
Trypsin premature activation has been thought to be a key event in the initiation phase of acute pancreatitis. Here we test a hypothesis that a sustained increase of cytosolic Ca(2+) concentration ([Ca(2+)](C)) can trigger K(+) influx into pancreas acinar zymogen granules (ZGs) via a Ca(2+)-activated K(+) channel (K(Ca)), and this influx of K(+) then mobilizes bound-Ca(2+) by K(+)/Ca(2+) ion-exchange to increase free Ca(2+) concentration in the ZGs ([Ca(2+)](G)) and release bound-H(+) by K(+)/H(+) ion-exchange to decrease the pH in ZGs (pH(G)). Both the increase of [Ca(2+)](G) and the decrease of pH(G) will facilitate trypsinogen autoactivation and stabilize active trypsin inside ZGs that could lead to acute pancreatitis. The experimental results are consistent with our hypothesis, suggesting that K(+) induced ion-exchanges play a critical role in the initiation of trypsin premature activation in ZGs.
Yang
Kai
K
Department of Biological Sciences, Florida State University, Tallahassee, FL 32310, USA.
Ding
Yong-Xue
YX
Chin
Wei-Chun
WC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
D004792:Enzyme Precursors; D014357:Trypsin; D011188:Potassium; D002118:Calcium