CALCIUM SOURCE DIVERSITY IN CANINE LOWER ESOPHAGEAL SPHINCTER MUSCLE

Tonic contraction of the lower esophageal sphincter (LES) prevents gas troesophageal reflux. LES tone is produced both by cholinergic nerve a nd myogenic activities. The Ca++ sources for LES tone and carbachol-in duced 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 respectiv ely, and/or inhibition of Ca++ store refilling using the sarcoplasmic reticulum Ca++ pump inhibitor, cyclopiazonic acid. LES tone disappeare d when a Cafe-free physiological saline solution or nifedipine was app lied. Sustained Ca++ free contractions to carbachol were prevented/abo lished by nifedipine or increased Ca++ chelation and enhanced by BayK8 644. Inhibition of sarcoplasmic reticulum Ca++ pumps by cyclopiazonic acid reduced Ca++ free contractions to carbachol; BayK8644 restored cy clopiazonic acid-reduced Ca++ free contractions to carbachol. Therefor e, some Ca++ stores can be refilled by mechanisms not requiring activi ty of the sarcoplasmic reticulum Ca++ pump. A preferred pathway may ex ist whereby Ca++ enters stores directly through L-Ca++ channels. The p roposed 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 depende nt on Ca++ influx through L-Ca++ channels.