The effect of extracellular Cl (Cl(o)-) removal on contractions evoked by a selective muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl 1,3-dioxolane methiodide (CD), and high K+ depolarizations in the isolated guinea pig ileal longitudinal muscle was studied. The replacement of Cl(o)- with impermeant anions, such as isethionate (Ise-), was found to selectively inhibit a portion of the initial phasic response to K+ and CD, leaving the secondary and sustained tonic responses unchanged. In Ca2+-free solutions, the loss of contractile responses to high K+ was faster and more pronounced in Cl--free compared with Cl--containing solutions. Furthermore, the uptake of Ca2+, as represented by 45Ca2+, from the saline solution was delayed and reduced in Ise--containing Cl(o)--free solutions. Replacement of Cl(o)- with other impermeant anions, such as gluconate and methylsulphate, had a similar action on contractile activity as for Ise- replacement. Cl(o)- replacement with permeant anions, such as nitrate, however, did not significantly inhibit the phasic response and sometimes incrreased the tonic response to K+. These results indicate that there is a Cl(o)--dependent Ca2+ pool in the guinea pig ileal longitudinal muscle and we speculate that this Cl(o)--dependent Ca2+ pool is associated with membrane structures, such as calveolae, which would thus offer a degree of protection to depletion by removal of extracellular Ca2+. Overall, these data suggest that agonist responses in guinea pig ileal longitudinal muscle preparations utilize at least three Ca2+ pools: a Cl(o)--sensitive pool supplying Ca2+ primarily for phasic contractions, a Cl(o)--insensitive pool supplying Ca2+ for tonic and phasic contractions, and an extracellular pool that is most sensitive to organic Ca2+ channel antagonists such as D-600 and supplies Ca2+, presumably entering the cell through voltage-operated Ca2+ channels, for the tonic contractions.
|Number of pages||7|
|Journal||Canadian Journal of Physiology and Pharmacology|
|Publication status||Published - 1986|
ASJC Scopus subject areas
- Physiology (medical)