Norepinephrine acts on the K-ATP 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 ef fects of NE on [Ca2+](i) in individual HIT-T15 cells loaded with indo 1. Ce lls 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 [C a2+](i) in non-oscillators. In oscillators, NE decreased the amplitude and frequency of the oscillations. Furthermore, the duration of the NE effect i n oscillators was longer than in non-oscillators, NE did not affect the ris e in [Ca2+](i) elicited by depolarizing concentrations of 20 mM or 35 mM KC l alone, or in the presence of 20 mM KCl, 100 mu M diazoxide, and 10 mM glu cose. In other experiments, NE had no effect on [Ca2+](i) when the K-ATP ch annels were fully clamped with diazoxide or tolbutamide. We conclude that t he action of NE to decrease [Ca2+](i) in both oscillators and non-oscillato rs is mediated via activation of the K-ATP channel. Despite this common mec hanism, NE exerts different effects on oscillating and non-oscillating cell s. (C) 2000 Harcourt Publishers Ltd.