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Published on: June 25, 2014
TRPM4 controls insulin secretion in pancreatic beta-cells
Henrique Cheng1, Andreas Beck, Pierre Launay
1Laboratory of Cell and Molecular Signaling, Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine at the University of Hawaii, 1301 Punchbowl Street, UHT 8, Honolulu, HI 96813, USA.
Cell Calcium
|June 30, 2006
Summary
Transient Receptor Potential Melastatin 4 (TRPM4) channels in pancreatic beta-cells regulate insulin secretion by controlling cell depolarization. TRPM4
Area of Science:
- Cellular physiology
- Ion channel function
- Endocrinology
Background:
- Transient Receptor Potential Melastatin 4 (TRPM4) channels are calcium-activated non-selective cation channels implicated in cell depolarization.
- In excitable cells, TRPM4 channels may modulate calcium influx by influencing voltage-dependent calcium channel activation.
Purpose of the Study:
- To investigate the role of TRPM4 channels in insulin-secreting cells.
- To characterize TRPM4 channel activity and its regulation in pancreatic beta-cells.
Main Methods:
- Electrophysiological recordings in INS-1 cells and HEK-293 cells.
- Expression of dominant-negative TRPM4 constructs.
- Measurement of insulin secretion in response to glucose and arginine vasopressin.
- Cell capacitance measurements and FM1-43 dye uptake assays.
Main Results:
- INS-1 cells natively express functional TRPM4 channels that generate calcium-activated depolarizing currents.
- Suppression of TRPM4 activity significantly reduced glucose- and arginine vasopressin-stimulated insulin secretion.
- TRPM4 channel recruitment to the plasma membrane occurs in two phases: immediate plasma membrane activation and a secondary phase involving vesicle recruitment during exocytosis.
Conclusions:
- TRPM4 channels play a critical role in regulating membrane potential and electrical activity in secretory cells.
- Dynamic translocation of TRPM4 from vesicular stores to the plasma membrane via calcium-dependent exocytosis is a key regulatory mechanism for cellular electrical activity and insulin secretion.
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