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Ca2+ channel blockers inhibit secretory C1-channels in intestinal epithelial cells
G Champigny1, B Verrier, M Lazdunski
1Institut de Pharacologie moléculaire et cellulaire, Valbonne, France.
Abstract:
Outwardly rectifying Cl- channels are present in the human colonic cell line (HT29D4). The classical Cl- channel blocker 5-nitro-2(3-phenylpropylamino)benzoate inhibits Cl- channel activity with a K0.5 value of 20 microM. Epithelial Cl- channel activity is inhibited by Ca2+ channel blockers. Phenylalkylamines are the most effective inhibitors. (+/-)Verapamil and (-)desmethoxyverapamil induce flickering and then the complete blockade of Cl- channels recorded from outside-out patches. K0.5 values are 60 microM and 100 microM for (-)desmethoxyverapamil and (+/-)verapamil, respectively. Other classes of L-type Ca2+ channel blockers have also been studied but they are less active.
Insights
Human colonic cells possess outwardly rectifying chloride channels. These channels are inhibited by calcium channel blockers, particularly phenylalkylamines like verapamil.
Area of Science:
- Cell biology
- Ion channel physiology
- Pharmacology
Background:
- Outwardly rectifying chloride channels (CLA-) are present in the human colonic cell line HT29D4.
- Epithelial ion transport is crucial for colonic function.
Purpose of the Study:
- To investigate the pharmacological properties of outwardly rectifying chloride channels in HT29D4 cells.
- To determine the effect of calcium channel blockers on these chloride channels.
Main Methods:
- Patch-clamp electrophysiology was used to record chloride channel activity.
- The effects of various chloride and calcium channel blockers were assessed.
Main Results:
- The classical chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoate inhibited activity with a K0.5 of 20 microM.
- Calcium channel blockers, especially phenylalkylamines, inhibited epithelial chloride channel activity.
- (+/-)Verapamil and (-)desmethoxyverapamil induced flickering and complete blockade of chloride channels with K0.5 values of 100 microM and 60 microM, respectively.
Conclusions:
- Outwardly rectifying chloride channels in HT29D4 cells are modulated by calcium channel blockers.
- Phenylalkylamines represent a potent class of inhibitors for these chloride channels, suggesting a potential link between calcium and chloride transport pathways.