MEMBRANE POTENTIAL MEASUREMENTS IN ISLETS OF LANGERHANS FROM ob/ob OBESE MICE SUGGEST AN ALTERATION IN [Ca2+]i‐ACTIVATED K+ PERMEABILITY

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Abstract
High‐resistance micro‐electrodes were used to measure membrane potentials in β‐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 β‐cells, although similar to the burst pattern recorded from normal β‐cells, presents important differences. The membrane potential of the ob/ob β‐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 β‐cells. However, the average active‐phase duration is 20 s in ob/ob β‐cells compared with 5 s in normal β‐cells. The average burst frequency is 1·8 bursts/min in ob/ob β‐cells compared with 3 bursts/min in normal β‐cells. While normal β‐cells show continuous spike activity above 16 mM glucose, ob/ob β‐cells often exhibit a burst pattern of electrical activity at glucose concentrations as high as 33 mM. Compared with normal β‐cells, the relationship between spike frequency and glucose concentration is shifted towards lower concentrations in ob/ob β‐cells. Thus, the concentration for half‐maximal spike frequency is 6·9 mM for the ob/ob β‐cells and 10·2 mM for the normal β‐cells. In ob/ob β‐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 β‐cells. The modified pattern of response to glucose and decreased sensitivity to quinine and glibenclamide suggest that the β‐cell membrane of the ob/ob islet of Langerhans has a modified [Ca2+]i‐activated K+ permeability.