Effects of lowering external Na+ concentration on cytoplasmic pH and Ca2+ concentration in mouse pancreatic beta-cells: mechanism of periodicity of spike-bursts.
The periodic spike-burst response of pancreatic beta-cells varies in duration with an increase of external glucose within the range 5-20 mM. To elucidate the mechanism determining the length of spike-burst, we studied the low-Na+ induced change in electrical response to glucose which is similar to the change induced by high glucose. Cytoplasmic pH (pHi) and Ca2+ concentration ([Ca2+]i) were measured by the microfluorometric method under normal and low-Na+ conditions in mouse pancreatic islets. Lowering external Na+ concentration from 135 to 25 mM by replacing Na+ with Tris+ induced progressive alkalinization in islet cells in the presence of 11.1 mM glucose. In contrast, reduction of external Na+ by replacement with Li+ caused intracellular acidification. Both manipulations described above caused a marked increase in [Ca2+]i, suggesting the presence of Na+/Ca(2+)-antiport activity. Although the change in pHi induced by decreasing external Na+ varied in direction depending on the species of cations used for replacing Na+, the pattern of electrical activity consistently changed from the spike-burst type to the continuous spike-generation type without regard for the difference in species of cations replacing Na+. These findings lead to the following hypothesis: A decrease in Na+ influx could cause a decrease in ATP-consumption by Na+/K(+)-pumps that prevents the fall of intracellular ATP concentration. The resultant continuation of high concentrations of intracellular ATP may be responsible for the abolishment of the silent phase.
Hattori
M
M
Department of Physiology, Shiga University of Medical Science, Ohtsu, Japan.
Kai
R
R
Kitasato
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003592:Cytophotometry; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D011188:Potassium; D002118:Calcium