Oxidative stress increases potassium efflux from pancreatic islets by depletion of intracellular calcium stores.
Oxidative stress to B-cells is thought to be of relevance in declining B-cell function and in the process of B-cell destruction. In other tissues including heart, brain and liver, oxidative stress has been shown to elevate the intracellular free calcium concentration and to provoke potassium efflux. We studied the effect of oxidative stress on Ca2+ and K+ (Rb+) outflow from pancreatic islets using the thiol oxidants DIP and BuOOH. Both compounds reversibly increased 86Rb+ efflux in the presence of 3 and 16.7 mmol/l glucose. Stimulation of 86Rb+ efflux was also evident in the absence of calcium. DIP evoked release of 45Ca2+ from the pancreatic islets both in the presence or absence of extracellular calcium. Employing inhibitors of the calcium-activated potassium channel (KCa) and the high conductance K+-channel (BKCa), the effect of DIP on 86Rb+ efflux was slightly diminished. Tolbutamide had no effect on 86Rb+ efflux in the presence of DIP. On the other hand thapsigargin, a blocker of the Ca+-ATPase of the endoplasmic reticulum, completely suppressed the DIP-mediated 86Rb+ outflow. The data suggest that thiol oxidant-induced potassium efflux from pancreatic islets is mainly mediated through liberation of intracellular calcium and subsequent stimulation of calcium-activated potassium efflux.
Hennige
A M
AM
Department of Pharmacology, Institute of Pharmaceutical Sciences, University of Tübingen, Germany.
Lembert
N
N
Wahl
M A
MA
Ammon
H P
HP
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002463:Cell Membrane Permeability; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D001391:Azo Compounds; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; C013475:diazenedicarboxylic acid bis(N'-methylpiperazide); D000244:Adenosine Diphosphate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium