PT  - JOURNAL ARTICLE
AU  - Anne Marie F. Salapatek
AU  - Annette Lam
AU  - Edwin E. Daniel
TI  - Calcium Source Diversity in Canine Lower Esophageal Sphincter Muscle
DP  - 1998 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 98--106
VI  - 287
IP  - 1
4099  - http://jpet.aspetjournals.org/content/287/1/98.short
4100  - http://jpet.aspetjournals.org/content/287/1/98.full
SO  - J Pharmacol Exp Ther1998 Oct 01; 287
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics