Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreatic β-cells
10.16438/j.0513-4870.2023-0477
- VernacularTitle:TRPM4通道抑制剂9-菲酚对胰岛β细胞INS-1电活动的抑制作用
- Author:
Hui-fang LIU
;
Cong-xiao ZHANG
;
Ke-wei WANG
- Publication Type:Research Article
- Keywords:
9-phenanthrol;
transient receptor potential melastatin 4 channel;
hole-cell current clamp;
pancreatic β-cell;
action potential
- From:
Acta Pharmaceutica Sinica
2023;58(10):3059-3064
- CountryChina
- Language:Chinese
-
Abstract:
The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.
