Myenteric denervation of rat jejunum alters calcium responsiveness of intestinal smooth muscle

Abstract

Background/Aims: Long-term myenteric and extrinsic denervation of a segment of rat jejunum results in increased stress generation by the longitudinal muscle layer of the denervated segment 15 days after denervation. This study examined whether alterations in the properties of either cell membrane calcium channels and/or sarcoplasmic reticular Ca 2+-adenosine triphosphatase (ATPase) contribute to the increased stress development. Methods: The effects of the calcium channel blocker nifedipine and the sarcoplasmic reticular Ca 2+-ATPase inhibitor cyclopiazonic acid on the contractile activity of denervated and control smooth muscle were determined. Results: The ability of nifedipine to inhibit KCl-induced contractions was significantly increased in denervated tissues; however, there was no difference in the potency of nifedipine when tissues were stimulated with carbachol. Calcium concentration-response curves obtained in the presence of either KCl or carbachol were determined in tissues previously depleted of calcium. Long-term denervated tissues showed an increased sensitivity to calcium and a decreased maximum contractile response after stimulation with carbachol. Cyclopiazonic acid inhibited repletion of intracellular calcium stores of control muscle but had no effect in denervated tissue. Conclusions: Long-term denervation of a segment of rat small intestine results in profound alterations in calcium metabolism at the cell membrane and, to a lesser extent, at the sarcoplasmic reticulum of smooth muscle cells of the longitudinal muscle layer.