Effect of trimebutine on K+ current in rabbit ileal smooth muscle cells

Area of Science:

• Pharmacology
• Gastroenterology
• Ion Channel Physiology

Background:

• Trimebutine is a spasmolytic agent used for gastrointestinal disorders.
• The precise cellular mechanisms underlying trimebutine's effects on smooth muscle are not fully elucidated.
• Potassium (K+) currents play a crucial role in regulating smooth muscle excitability.

Purpose of the Study:

• To investigate the effects of trimebutine on K+ currents in rabbit ileal smooth muscle cells.
• To determine the specific K+ current subtypes affected by trimebutine.
• To elucidate the relationship between trimebutine's action on K+ currents and its gastrointestinal effects.

Main Methods:

• Whole-cell patch-clamp technique applied to isolated rabbit ileal smooth muscle cells.
• Application of varying concentrations of trimebutine (1-100 microM).
• Electrophysiological recordings to measure K+ currents (IKCa and IKv) and spontaneous transient outward currents.

Main Results:

• Trimebutine inhibited both Ca(2+)-dependent K+ current (IKCa) and Ca(2+)-independent K+ current (IKv).
• Dose-dependent inhibition was observed with IC50 values of 7.6 microM for IKv and 23.5 microM for IKCa.
• Trimebutine decreased the amplitude and discharge rate of spontaneous transient outward currents.
• A 30 microM concentration of trimebutine caused membrane depolarization and decreased membrane conductance.

Conclusions:

• Trimebutine exerts its effects by inhibiting K+ currents in the ileal smooth muscle.
• The inhibition of IKv and IKCa contributes to the modulation of smooth muscle excitability.
• These findings suggest that trimebutine's excitatory effects on the gastrointestinal tract are mediated by its action on K+ channels.