Membrane potential measurements in islets of Langerhans from ob/ob obese mice suggest an alteration in [Ca2+]i-activated K+ permeability.
High-resistance micro-electrodes were used to measure membrane potentials in beta-cells from islets of Langerhans of ob/ob obese mice (Norwich colony). In the presence of glucose the burst pattern of electrical activity recorded in ob/ob beta-cells, although similar to the burst pattern recorded from normal beta-cells, presents important differences. The membrane potential of the ob/ob beta-cells in the presence of 11 mM glucose in the modified Krebs solution oscillates between a silent-phase level at -48 mV and an active-phase level at -36 mV, similarly to normal mouse islet beta-cells. However, the average active-phase duration is 20 s in ob/ob beta-cells compared with 5 s in normal beta-cells. The average burst frequency is 1.8 bursts/min in ob/ob beta-cells compared with 3 bursts/min in normal beta-cells. While normal beta-cells show continuous spike activity above 16 mM glucose, ob/ob beta-cells often exhibit a burst pattern of electrical activity at glucose concentrations as high as 33 mM. Compared with normal beta-cells, the relationship between spike frequency and glucose concentration is shifted towards lower concentrations in ob/ob beta-cells. Thus, the concentration for half-maximal spike frequency is 6.9 mM for the ob/ob beta-cells and 10.2 mM for the normal beta-cells. In ob/ob beta-cells, the mitochondrial inhibitor carbonyl-cyanide m-chlorophenylhydrazone induces hyperpolarization of the membrane, consistent with its effect of stimulating K+ permeability in normal islets. However, quinine and the sulphonylurea glibenclamide did not block the silent phase between the bursts of electrical activity. Both drugs block the [Ca2+]i-activated K+ permeability thought to control the membrane potential at the silent phase in normal beta-cells. The modified pattern of response to glucose and decreased sensitivity to quinine and glibenclamide suggest that the beta-cell membrane of the ob/ob islet of Langerhans has a modified [Ca2+]i-activated K+ permeability.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002463:Cell Membrane Permeability; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology; D012016:Reference Values
D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011803:Quinine; D005947:Glucose; D011188:Potassium; D005905:Glyburide; D002118:Calcium