An increase in plasma glucose concentration stimulates insulin secretion by causing a depolarisation of β-cell membrane potential. The closure of K_ATP channels is a major factor in the depolarisation, but the activation of anion channels may also contribute (Best et al. 1997). By contrast to β-cells, glucagon secretion from α-cells is inhibited by an increase in plasma glucose (Best & McLaughlin, 2003). We are currently investigating the hypothesis that the activation of volume-activated anion channels by glucose, causes a hyperpolarisation of the α-cell membrane potential and a depolarisation of the β-cell.

To test this hypothesis, the expression of cation-chloride transporters in cells of the pancreatic islets has been investigated. Islet cells were isolated from the pancreas of rats which had been killed by inhalation of an overdose of halothane . In β-cells there is functional and immunocytochemical evidence for the expression of NKCC1 (Majid et al. 2001). NKCC1 is not, however, expressed in α-cells. Thus, NKCC1 (a Cl^– accumulator) is expressed in cells in which Cl^– is above equilibrium, i.e. activation of anion channels is excitatory. RT-PCR has demonstrated the expression of mRNA for KCC3a, KCC3b and KCC4 in pancreatic islet cells. Cell volume studies suggest that these KCCs are expressed in α-cells, but not β-cells (Davies et al. 2002). This conclusion is supported by preliminary immunocytochemical data, which show that the KCC proteins are coexpressed with glucagon, but not insulin or somatostatin. These data therefore indicate that KCCs (Cl^– extruders) are expressed in the α-cells, in which Cl^– must be below equilibrium, i.e. activation of Cl^– channels is inhibitory.

In conclusion, KCCs are expressed in α-cells and NKCC1 in β-cells. The data are therefore consistent with the different putative roles of anion channels in these cells.