Background: 

Glucose-induced electrical activity of beta-cells within an islet of Langerhans consists of slow waves, i.e. oscillations of the membrane potential (V_m) (bursts and interbursts). Slow waves drive oscillations of the cytosolic Ca²⁺ concentration ([Ca²⁺]_c) and insulin secretion at glucose concentrations between ~6 and 20 mM. Since more than forty years the fraction of plateau phase (FOPP), i.e. the percentage of time with bursts, is an excellent marker of beta-cell function and activity. So far all tools to measure the FOPP require high technical skills and/or interfere themselves with beta-cell function.

Methodology: 

Whole mouse islets were arranged on an electrode of a microelectrode array (MEA). Extracellular voltage changes were measured allowing the detection of burst and interburst phases.

Results: 

At a non-stimulating glucose concentration (3 mM, n=10) no electrical activity was detectable while continuous bursting appeared at 30 mM (n=5). The glucose concentration-response curve reveals half-maximal stimulation at 12±2 mM. The signal was sensitive to the K_ATP channel modulators tolbutamide or diazoxide. TRAM-34 (1 mM, n=9) led to an increase in activity due to prolongation of the burst phases indicating an important role of SK4 channels in the oscillatory pattern.

Conclusion: 

The glucose responsiveness of the extracellular recordings is consistent with that of intracellular measurements. The results provide a 'proof-of-principle' for detection and determination of beta-cell oscillations and the FOPP with extracellular electrodes on a MEA based system. This easy-to-use method may serve as a high-throughput tool in industrial and academical research or as a functionality test for islets prone to transplantation.