Differential modulation of pancreatic β‐cell bursting by intracellular pH in the presence and absence of a K‐ATP channel blocker

[摘要]

The study of the influence of intracellular pH (pH_i) changes on the mechanism underlying pancreatic β-cell bursting has been hampered by concomitant effects on the activity of background ATP-dependent K⁺ (K-ATP) channels. β-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 pH; shift (exposure to 20 mM NH₄C1) 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 β-cell ion channels to pH_i and the prevalent role of K-ATP channels as electrical transducers of cytoplasmic pH changes under regular physiological conditions.

[学科分类] 生物化学/生物物理

[关键词] Pancreatic β-cell;Islet of Langerhans;Intracellular pH;Bursting electrical activity;ATP-dependent K+ channel;Extracellular Ca2+;pHi;intracellular pH;K-ATP channels;ATP-dependent K+ channels;K-Ca channels;Ca2+-activated K+ channels;[Ca2+]i;intracellular free Ca2+ concentration;BCECF;2';7'-bis-carboxyethyl-5(6)-carboxyfluorescein;BCECF/AM;acetoxymethyl ester of BCECF