Calcium source diversity in canine lower esophageal sphincter muscle

Tonic contraction of the lower esophageal sphincter (LES) prevents gastroesophageal reflux. LES tone is produced both by cholinergic nerve and myogenic activities. The Ca++ sources for LES tone and carbachol-induced contraction in canine LES strips were determined from the effect on contractile activity of extracellular Ca++ level modulation, Ca++ entrance blockade or enhancement with nifedipine or BayK8644 respectively, and/or inhibition of Ca++ store refilling using the sarcoplasmic reticulum Ca++ pump inhibitor, cyclopiazonic acid. LES tone disappeared when a Ca++-free physiological saline solution or nifedipine was applied. Sustained Ca++ free contractions to carbachol were prevented/abolished by nifedipine or increased Ca++ chelation and enhanced by BayK8644. Inhibition of sarcoplasmic reticulum Ca++ pumps by cyclopiazonic acid reduced Ca++ free contractions to carbachol; BayK8644 restored cyclopiazonic acid-reduced Ca++ free contractions to carbachol. Therefore, some Ca++ stores can be refilled by mechanisms not requiring activity of the sarcoplasmic reticulum Ca++ pump. A preferred pathway may exist whereby Ca++ enters stores directly through L-Ca++ channels. The proposed Ca++ store refilling mechanism involves continuous Ca++ entry through L-Ca++ channels from sites not equilibrated with external Ca++. Therefore, diverse Ca++ stores exist in canine LES which are dependent on Ca++ influx through L-Ca++ channels.