Ca2+ handling of rat pancreatic beta-cells exposed to ryanodine, caffeine, and glucagon.

Reported species differences in the stimulus-secretion coupling of insulin release made it important to compare the Ca2+ handling of rat beta-cells with that previously observed in mice. Single beta-cells and small aggregates were prepared from pancreatic islets of Wistar rats, attached to cover slips and then used for measuring the cytoplasmic Ca2+ concentration ([Ca2+]i) with the ratiometric fura-2 technique. Glucose (11 mM) induced slow oscillations of [Ca2+]i similar to those seen in other species, including humans. Comparison of the oscillations in rat beta-cells with those previously described in mouse revealed that there was a slightly lower frequency and an increased tendency to transformation into sustained [Ca2+]i in response to glucagon or caffeine. Ryanodine (5-20 microM) did not affect existing oscillations but sometimes restored rhythmic activity in the presence of caffeine. Stimulation with glucose resulted not only in oscillations but also in transients of [Ca2+]i sometimes appearing in synchrony in adjacent beta-cells and disappearing after the addition of 200 nM thapsigargin or 20 mM caffeine. The frequency of transients recorded in a medium containing glucagon and methoxyverapamil was higher than seen under similar conditions in mouse beta-cells. Although exhibiting some differences compared with mouse beta-cells, rat beta-cells also have an intrinsic ability to oscillate and to generate the transients of [Ca2+] that are supposed to synchronize the rhythmicity of the islets in the pancreas.