Background:

Glucose-induced electrical activity of beta-cells is essential for proper insulin secretion. Electrical activity is characterized by oscillations between depolarized phases with action potentials and silent interburst phases, quantified as fraction of plateau phase (FOPP) i.e. fraction of time with spike activity. Recently we have shown that a microelectrode array (MEA) is a new rapid approach to measure beta-cell electrical activity. With MEAs glucose-dependency of electrical activity could be resolved as precisely as with classical microelectrodes. Here we demonstrate that this method is extremely useful to address physiological, pathophysiological, and pharmacological questions in beta-cell research.

Methodology:

Isolated islets of adult mice were either acutely placed or cultured onto MEAs. Extracellular voltage changes were measured non-invasively at 37°C.

Results:

A pharmacological inhibitor of SK4 channels (TRAM34, 1µM), increased the FOPP by 24% (n=5) supporting the hypothesis that SK4 channels play a critical role in oscillatory activity. Induction of oxidative stress by 300 µM H₂O₂ decreased the FOPP by 25% (n=14) at 10 mM glucose and diminished glucose-induced insulin secretion. Preincubation of islets with tempol, a superoxide dismutase mimetic, protected beta-cells against oxidative stress by restoring the FOPP and insulin release. Development of an islet culture on MEAs allowed to record electrical activity over several weeks (n=29) giving rise to a new approach to study islet physiology in long-term in vitro experiments.

Conclusion:

The MEA technology is a simple and reliable method to detect small changes in beta-cell electrical activity. One strength of the technique is its possible application in long-term experiments.