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Vol. 287, Issue 1, 98-106, October 1998
Department of Biomedical Sciences, McMaster University, Faculty of
Health Sciences, Hamilton, Ontario L8N 3Z5, Canada
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.
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