Glucose and pharmacological modulators of ATP-sensitive K+ channels control [Ca2+]c by different mechanisms in isolated mouse alpha-cells.

OBJECTIVE

We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell Ca(2+).

RESEARCH DESIGN AND METHODS

GYY mice (expressing enhanced yellow fluorescent protein in alpha-cells) and NMRI mice were used. Ca(2+), the K(ATP) current (I(KATP), perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single alpha-cells and, for comparison, in single beta-cells.

RESULTS

In 0.5 mmol/l glucose, Ca(2+) oscillated in some alpha-cells and was basal in the others. Increasing glucose to 15 mmol/l decreased Ca(2+) by approximately 30% in oscillating cells and was ineffective in the others. alpha-Cell I(KATP) was inhibited by tolbutamide and activated by diazoxide or the mitochondrial poison azide, as in beta-cells. Tolbutamide increased alpha-cell Ca(2+), whereas diazoxide and azide abolished Ca(2+) oscillations. Increasing glucose from 0.5 to 15 mmol/l did not change I(KATP) and NAD(P)H fluorescence in alpha-cells in contrast to beta-cells. The use of nimodipine showed that L-type Ca(2+) channels are the main conduits for Ca(2+) influx in alpha-cells. gamma-Aminobutyric acid and zinc did not decrease alpha-cell Ca(2+), and insulin, although lowering Ca(2+) very modestly, did not affect glucagon secretion.

CONCLUSIONS

alpha-Cells display similarities with beta-cells: K(ATP) channels control Ca(2+) influx mainly through L-type Ca(2+) channels. However, alpha-cells have distinct features from beta-cells: Most K(ATP) channels are already closed at low glucose, glucose does not affect cell metabolism and I(KATP), and it slightly decreases Ca(2+). Hence, glucose and K(ATP) channel modulators exert distinct effects on alpha-cell Ca(2+). The direct small glucose-induced drop in alpha-cell Ca(2+) contributes likely only partly to the strong glucose-induced inhibition of glucagon secretion in islets.