The RESPONSE OF PANCREATIC Β‐CELL MEMBRANE POTENTIAL TO POTASSIUM‐INDUCED CALCIUM INFLUX IN THE PRESENCE OF GLUCOSE

Abstract

SUMMARYMembrane potential measurements were made in pancreatic f-cells from microdissected islets from normal mice. In the presence of 11 mm glucose, depolarization of the membrane for 1 min with 50 mm potassium is followed by an inhibition of electrical activity before the normal burst pattern resumes. This inhibitory period, called the recovery time, is steady for each f-cell after three consecutive pulses of 50 mm potassium. The mean recovery time is 109 s. During the recovery time, the membrane is hyperpolarized and the input resistance is decreased, indicating that potassium permeability is high over this period. The recovery time is dependent on the size of the depolarization: 1 min exposure to potassium concentrations below 50 mm reduces the recovery time with a half-maximal effect at 38-5 mm potassium, corresponding to -27 mV. Also, increasing the extracellular calcium concentration lengthens the recovery time. Increasing the glucose concentration, however, shortens the recovery time. It is postulated that the recovery time represents activation of the calcium-gated potassium permeability and is a reflexion of the time taken for the fl-cell to buffer the increased intracellular calcium resulting from the potassium depolarization.

Dual Functional Role of Membrane Depolarization/Ca2+ Influx in Rat Pancreatic B-Cell

“…The activation of K + ATP channel-independent, glucose-responsive effector by membrane depolarization was clearly detectable with a lower (25-mM) K + concentration as well. This finding implies that weaker membrane depolarization induced by 25 mM K + than that produced by [K + 50 ] (4,13) possesses such a role, although 25 mM K + causes significant depolarization of the B-cell compared with the normal basal membrane potentials (26). We tried to delineate the nature of K + ATP channel-independent, glucose-responsive effector in the following experiments; however, it remains unestablished (see below).…”

Organelle Selection Determines Agonist-specific Ca2+ Signals in Pancreatic Acinar and β Cells

“…In the ␤ cell line, MIN6 (16), we compared three different stimuli, glucose, acetylcholine, and K ϩ , with regard to their relative sensitivities to bafilomycin A1 or thapsigargin. Mechanistically, glucose metabolism generates intracellular signals that culminate in a complex interplay between Ca 2ϩ influx and Ca 2ϩ release from intracellular stores (17); muscarinic acetylcholine receptors are G protein-coupled to phospholipase C (15), whereas high K ϩ depolarizes the plasma membrane to induce voltage-operated Ca 2ϩ entry (18,19) In MIN6 cells, the sensitivity of Ca 2ϩ responses to bafilomycin A1 was, like acinar cells, highly dependent upon the stimulus. Remarkably glucose responses were profoundly inhibited by a preincubation with bafilomycin A1 (Fig.…”

“…1) (22). More surprisingly, glucose-stimulated Ca 2ϩ signals in ␤ cells also manifest a profound sensitivity to acidic store blockade when there ought to be a substantial residual Ca 2ϩ entry component (17,18) (and perhaps an ER component) (31). Although there is currently no complete mechanistic explanation for this absolute dependence, it has been empirically determined that desensitization of the NAADP receptor by its own ligand ablates both the cholecystokinin-as well as the glucose-induced Ca 2ϩ signals (16,22).…”

Modulation of K+ conductance by intracellular pH in pancreatic β‐cells

“…Activation of K+ conductance would induce a transition of the &cell membrane towards more negative potentials and would cause the end of the burst. This tentative explanation may also account for the undershoot of At, that preceded the recovery of electrical activity towards baseline (see fig.4) -a phenomenon that resembles the reduction of glucose-induced electrical activity induced by short exposures to a high-K+ solution [22].…”