Norepinephrine acts on the KATP channel and produces different effects on [Ca2+]i in oscillating and non-oscillating HIT-T15 cells.
Norepinephrine (NE) is an inhibitor of insulin secretion that acts, in part, by decreasing intracellular free calcium ([Ca2+]i). We examined the effects of NE on [Ca2+]i in individual HIT-T15 cells loaded with indo 1. Cells were categorized as oscillators or non-oscillators on the basis of the pattern of the calcium response to glucose and the effect of NE on [Ca2+]i was subsequently measured in each cell. NE caused a simple decrease in [Ca2+]i in nonoscillators. In oscillators, NE decreased the amplitude and frequency of the oscillations. Furthermore, the duration of the NE effect in oscillators was longer than in non-oscillators. NE did not affect the rise in [Ca2+]i elicited by depolarizing concentrations of 20 mM or 35 mM KCl alone, or in the presence of 20 mM KCl, 100 microM diazoxide, and 10 mM glucose. In other experiments, NE had no effect on [Ca2+]i when the KATP channels were fully clamped with diazoxide or tolbutamide. We conclude that the action of NE to decrease [Ca2+]i in both oscillators and non-oscillators is mediated via activation of the KATP channel. Despite this common mechanism, NE exerts different effects on oscillating and non-oscillating cells.
Schermerhorn
T
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Department of Molecular Medicine, College of Veterinary Medicine, Cornell University Ithaca, New York 14853, USA.
Sharp
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GW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006224:Cricetinae; D003592:Cytophotometry; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D002118:Calcium; D009638:Norepinephrine