Glucose-dependent regulation of rhythmic action potential firing in pancreatic beta-cells by K-ATP-channel modulation

• The regulation of a K+ current activating during oscillatory electrical activity (I-K,I-slow) in an insulin-releasing,beta-cell was studied by applying the perforated patch whole-cell technique to intact mouse pancreatic islets. The resting whole-cell conductance in the presence of 10 mm glucose amounted to 1.3 nS, which rose by 50% during a series of 26 simulated action potentials. Application of the K-ATP-channel blocker tolbutamide produced uninterrupted action potential firing and reduced IK,slow by similar to50%. Increasing glucose from 15 to 30 mm, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I-K,I-slow by similar to30% whilst not affecting the resting conductance. Action potential firing may culminate in opening of K-ATP channels by activation of ATP-dependent Ca2+ pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin (4 muM) inhibited I-K,I-slow by 25% and abolished bursting electrical activity. We conclude that oscillatory glucose-induced electrical activity in the beta-cell involves the opening of KATP-channel activity and that these channels, in addition to constituting the glucose-regulated K+ conductance, also play a role in the graded response to supra-threshold glucose concentrations.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

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