Ca(2+)-dependent Cl- current in canine tracheal smooth muscle cells

Area of Science:

• Physiology
• Cell Biology
• Pharmacology

Background:

• Smooth muscle cells regulate airway function.
• Chloride currents (ICl) play a role in smooth muscle cell excitability.
• Calcium (Ca2+) influx is a key signaling mechanism in muscle cells.

Purpose of the Study:

• To investigate the role of Ca2+ entry in regulating Cl- current (ICl) in canine trachealis smooth muscle cells.
• To determine if intracellular Ca2+ release is necessary for Ca2+-activated Cl- current (ICa(Ca)) activation.

Main Methods:

• Perforated patch-clamp electrophysiology was used to measure currents in smooth muscle cells.
• Pharmacological agents (niflumic acid, BAY K 8644, acetylcholine, nifedipine, cyclopiazonic acid) were employed to modulate ion channels and Ca2+ stores.
• Depolarization protocols were used to elicit Ca2+ currents (ICa).

Main Results:

• Depolarization activated a dihydropyridine-sensitive Ca2+ current (ICa) followed by a sustained Cl- current (ICl).
• The ICl was dependent on Ca2+ entry, increasing with augmented Ca2+ influx and decreasing with reduced influx.
• Ca2+ entry activated ICl even when intracellular Ca2+ stores were depleted, indicating Ca2+-induced Ca2+ release was not required.

Conclusions:

• Depolarization-induced Ca2+ entry activates Cl- channels in tracheal smooth muscle cells, a process termed ICl(Ca).
• This activation does not require Ca2+-induced Ca2+ release from intracellular stores.
• Ca2+ entry-mediated activation of ICl represents a positive-feedback mechanism that enhances airway smooth muscle excitation and contraction.