The ATP‐sensitive potassium channel in pancreatic B‐cells is inhibited in physiological bicarbonate buffer

FEBS Letters

Carroll, Patricia B.¹  Li, Min-Xu¹  Rojas, Eduardo¹  Atwater, Illani¹ 

[1] Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Building 8, Room 403, Bethesda, MD 20892, USA

关键词: Bicarbonate buffer;    K+-ATP channel;    K+-[Ca2+]i channel;    intracellular pH;    Glucose sensing;    (Pancreatic B-cell);   

DOI  :  10.1016/0014-5793(88)81335-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effects of bicarbonate buffer (HCO⁻ ₃/CO₂) on the activity of the two K⁺ channels proposed by some to control the pancreatic B-cell membrane response to glucose were studied. Single K⁺-channel records from membrane patches of cultured B-cells dissociated from adult rat islets exposed to a glucose- and bicarbonate-free medium (Na-Hepes in place of bicarbonate) exhibit the activity of both the ATP-sensitive as well as the [Ca²⁺]_i-activated K⁺ channels. However, in the presence of bicarbonate-buffered Krebs solution, the activity of the ATP-sensitive K⁺ channel is inhibited leaving the activity of the K⁺ channel activated by intracellular [Ca²⁺]_i unaffected. In the absence of bicarbonate (Hepes/NaOH in place of bicarbonate), lowering the external pH from 7.4 to 7.0 also has differential effects on the two K⁺ channels. While the K⁺ channel sensitive to ATP is inhibited, the K⁺ channel activated by a rise in [Ca²⁺]_i is not affected. To determine whether the response of the B-cell in culture to bicarbonate is also present when the B-cell is functioning within the islet syncytium, the effects of bicarbonate removal on membrane potential of B-cells from intact mouse islets were compared. These studies showed that glucose-evoked electrical activity is also blocked in bicarbonate-free Krebs solution. Furthermore, in the absence of bicarbonate and presence of glucose (11 mM), electrical activity was recovered by lowering the pH_o from 7.4 to 7.0. The ATP-sensitive K⁺-channel activity is greatly reduced by physiologically buffered solutions in pancreatic B-cells in culture. The most likely explanation for the bicarbonate effects is that they are mediated by cytosolic pH changes. Removal of bicarbonate (keeping the external pH at 7.4 with Hepes/NaOH as buffer) would increase the pH_i. Since the activity of the [Ca²⁺]_i-dependent K⁺ channels is not affected by the removal of the bicarbonate buffer, our patch-clamp data in cultured B-cells indicate an involment of [Ca²⁺]i-activated K⁺ channels in the control of the membrane potential. For the B-cell in the islet, we propose that the burst pattern of electrical activity (Ca²⁺ entry) is controlled, at least in part, by the [Ca²⁺]i-activated K⁺ channel.

【 授权许可】

Unknown