Ca2+ release-activated channels in rat stomach smooth muscle cells

Area of Science:

• Pharmacology
• Cell Physiology
• Gastroenterology

Background:

• Thapsigargin is a known inhibitor of the sarco/endoplasmic reticulum Ca2+-ATPase.
• Calcium signaling plays a crucial role in regulating smooth muscle contraction in the stomach fundus.

Purpose of the Study:

• To investigate the mechanism by which thapsigargin potentiates contractions in the rat stomach fundus.
• To determine the specific calcium channels involved in thapsigargin-induced potentiation.

Main Methods:

• Experiments were conducted on isolated rat stomach fundus and dissociated fundus cells.
• Contractions were induced by calcium (Ca2+), and intracellular calcium levels were measured.
• The effects of thapsigargin were assessed in the presence and absence of specific channel blockers, including CRAC channel blockers (miconazole, SK&F96365) and VOC channel blockers (isradipine).

Main Results:

• Thapsigargin strikingly potentiated Ca2+-induced contractions in rat stomach fundus.
• In dissociated cells, thapsigargin potentiated the rise in intracellular Ca2+ upon reintroduction of extracellular Ca2+.
• This potentiation was partially inhibited by CRAC channel blockers but only slightly affected by VOC channel blockers.

Conclusions:

• Thapsigargin increases calcium influx into rat stomach fundus cells.
• This influx is predominantly mediated by calcium-release-activated calcium channels (CRACs) following depletion of intracellular calcium stores.
• CRAC channels are key players in regulating gastric smooth muscle tone under conditions of intracellular calcium depletion.