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Effect of W-7 on ionic fluxes and electrical activity of mouse pancreatic islets
M A Wahl1, K A Spenny, H Safayhi
1Department of Pharmacology, Eberhard-Karls Universität Tübingen, F.R.G.
Abstract:
W-7 (N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide) (0.1 mM), a calmodulin inhibiting compound, suppressed the reincrease of 86Rb+ efflux from pancreatic islets normally seen in response to lowering the glucose concentration from stimulated to basal value. Ionophore (A23187)-induced increase was completely abolished. W-7 inhibited 45Ca2+ uptake and stimulation of 45Ca2+ efflux in response to glucose (11.1 mM) but did not affect K+ (20 mM)-induced 45Ca2+ uptake. Electrical activity of B-cells at 11.1 mM glucose showed a prolongation in burst length in the presence of 0.1 mM W-7. The data suggest that W-7 affects the opening properties of K+ channels resulting in a delayed repolarisation of the cells possibly through its inhibitory action on Ca2(+)-activated calmodulin.
Insights
Calmodulin inhibition by W-7 suppressed ion transport and altered pancreatic B-cell electrical activity. This suggests W-7 affects potassium channels and cell repolarization via calmodulin.
Area of Science:
- Endocrinology
- Cell Physiology
- Molecular Pharmacology
Background:
- Pancreatic islets regulate glucose homeostasis via ion channel activity.
- Calmodulin plays a role in cellular signaling pathways, including calcium and potassium transport.
Purpose of the Study:
- To investigate the effect of calmodulin inhibition on ion transport and electrical activity in pancreatic B-cells.
- To elucidate the role of calmodulin in glucose-stimulated insulin secretion.
Main Methods:
- Utilized 86Rubidium (86Rb+) and 45Calcium (45Ca2+) efflux assays to measure ion transport.
- Assessed pancreatic B-cell electrical activity using electrophysiological recordings.
- Employed W-7 (N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide), a calmodulin inhibitor.
Main Results:
- W-7 (0.1 mM) suppressed the reincrease of 86Rb+ efflux upon glucose reduction and abolished ionophore-induced efflux.
- W-7 inhibited glucose-stimulated 45Ca2+ uptake and efflux but did not affect K+-induced 45Ca2+ uptake.
- W-7 prolonged the burst length of B-cell electrical activity at 11.1 mM glucose.
Conclusions:
- Calmodulin inhibition by W-7 disrupts ion transport mechanisms in pancreatic islets.
- W-7 appears to affect K+ channel opening properties, leading to delayed repolarization.
- These findings suggest calmodulin's involvement in regulating B-cell electrical activity and ion flux.