GLUCOSE AND ALPHA-KETOISOCAPROATE INDUCE TRANSIENT INWARD CURRENTS INRAT PANCREATIC BETA-CELLS

The perforated patch technique was used to study changes in membrane p otential and whole-cell currents in single isolated rat pancreatic bet a-cells during stimulation with glucose or alpha-ketoisocaproate. Incr easing the glucose concentration from 4 to 20 mmol/l, or addition of 1 5 mmol/l alpha-ketoisocaproate, caused depolarization and, in most cas es, initiation of action potentials. Under voltage-clamp conditions cl ose to a potassium equilibrium potential (E(K)) (-60 to -70 mV) these effects were accompanied by the appearance of transient inward current s. These transient currents resembled those elicited during cell swell ing in response to a 10% hypotonic bath solution, a manoeuvre which al so caused beta-cell depolarization and electrical activity. Tolbutamid e (0.2 mmol/l), in the absence of glucose depolarized beta-cells but d id not induce transient inward currents. Nutrient-induced electrical a ctivity and inward currents were abolished by the anion channel inhibi tors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid and 5-nitro-2 -(3-phenylpropylamino) benzoic acid, compounds which also inhibited gl ucose-induced insulin release. It is concluded that nutrient secretago gues induce transient inward currents in isolated rat beta-cells, poss ibly by activating a volume-sensitive anion conductance. These inward currents could enhance the intensity of electrical, and hence secretor y, activity in the beta-cell during nutrient stimulation.