Differential modulation of pancreatic beta-cell bursting by intracellular pH in the presence and absence of a K-ATP channel blocker.
The study of the influence of intracellular pH (pHi) changes on the mechanism underlying pancreatic beta-cell bursting has been hampered by concomitant effects on the activity of background ATP-dependent K+ (K-ATP) channels. beta-cells were made to burst in the absence of active K-ATP channels by raising external Ca2+ in the presence of 11 mM glucose and tolbutamide. An alkalinizing pHi shift (exposure to 20 mM NH4Cl) increased the burst active phase duration. Conversely, an acidifying shift (NH4Cl withdrawal) suppressed the electrical activity. This is the mirror image of the effects recorded in the absence of tolbutamide. Glibenclamide and quinine suppressed the alkalinization-evoked hyperpolarization. This study emphasizes the differential sensitivity of different beta-cell ion channels to pHi and the prevalent role of K-ATP channels as electrical transducers of cytoplasmic pH changes under regular physiological conditions.
Barbosa
R M
RM
Department of Zoology, University of Coimbra, Portugal.
Salgado
A P
AP
Santos
R M
RM
Rosário
L M
LM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D026902:Potassium Channel Blockers
D005452:Fluoresceins; D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D000643:Ammonium Chloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D000255:Adenosine Triphosphate; D002118:Calcium