Dual effects of Na/K pump inhibition on cytoplasmic Ca2+ oscillations in pancreatic beta-cells.
Inhibition of the Na/K pump by ouabain or removal of K+ resulted in gradual increase of intracellular sodium in beta-cell-rich pancreatic islets from ob/ob-mice exposed to 3 mM glucose. In individual beta-cells this action of ouabain was paralleled by closure of ATP-regulated K+ channels and a slow elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i). In most beta-cells an increase of the glucose concentration to 11-20 mM induced large amplitude oscillations of [Ca2+]i with a frequency of 0.2-0.5/min. Ouabain had dual actions on these glucose-induced oscillations in promoting their appearance and at higher concentrations transforming them into a sustained increase of [Ca2+]i. At 100 microM ouabain reduced the frequency of the glucose-induced oscillations but nevertheless raised the time-average [Ca2+]i by increasing the amplitudes and half-widths of the Ca2+ peaks. When high concentrations of ouabain or removal of K+ transformed the oscillations into a sustained increase of [Ca2+]i, the level reached exceeded that obtained in response to rise of glucose alone. By favoring Ca2+ entry and counteracting removal of the cation from the cytoplasm, Na/K pump inhibition perturbs the balance between the processes determining glucose-induced oscillations of [Ca2+]i.
Grapengiesser
E
E
Department of Medical Cell Biology, Uppsala University, Sweden.
Berts
A
A
Saha
S
S
Lund
P E
PE
Gylfe
E
E
Hellman
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D009991:Oscillometry; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D013997:Time Factors
D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D011188:Potassium; D002118:Calcium