Acta Pharmacologica Sinica (2009) 30: 1421–1427; doi: 10.1038/aps.2009.123; published online 14 Sep 2009

Aim: To evaluate the impact of extracellular and intracellular Ca²⁺ on contractions induced by ethanol in smooth muscle.

Methods: Longitudinal smooth muscle strips were prepared from the gastric fundi of mice.  The contractions of smooth muscle strips were recorded with an isometric force displacement transducer.

Results: Ethanol (164 mmol/L) produced reproducible contractions in isolated gastric fundal strips of mice.  Although lidocaine (50 and 100 µmol/L), a local anesthetic agent, and hexamethonium (100 and 500 µmol/L), a ganglionic blocking agent, failed to affect these contractions, verapamil (1–50 µmol/L) and nifedipine (1–50 µmol/L), selective blockers of L-type Ca²⁺ channels, significantly inhibited the contractile responses of ethanol.  Using a Ca²⁺-free medium nearly eliminated these contractions in the same tissue.  Ryanodine (1–50 µmol/L) and ruthenium red (10–100 µmol/L), selective blockers of intracellular Ca²⁺ channels/ryanodine receptors; cyclopiazonic acid (CPA; 1–10 µmol/L), a selective inhibitor of sarcoplasmic reticulum (SR) Ca²⁺-ATPase; and caffeine (0.5–5 mmol/L), a depleting agent of intracellular Ca²⁺ stores, significantly inhibited the contractile responses induced by ethanol.  In addition, the combination of caffeine (5 mmol/L) plus CPA (10 µmol/L), and ryanodine (10 µmol/L) plus CPA (10 µmol/L), caused further inhibition of contractions in response to ethanol.  This inhibition was significantly different from those associated with caffeine, ryanodine or CPA.  Furthermore the combination of caffeine (5 mmol/L), ryanodine (10 µmol/L) and CPA(10 µmol/L) eliminated the contractions induced by ethanol in isolated gastric fundal strips of mice. 

Conclusion: Both extracellular and intracellular Ca²⁺ may have important roles in regulating contractions induced by ethanol in the mouse gastric fundus.

Keywords: ethanol; contraction; smooth muscle; verapamil; nifedipine; ryanodine receptors; ryanodine; ruthenium red; caffeine