Impairment of Ca21 mobilization in circular muscle cells of the inflamed colon

Shi, Xuan-Zheng, and Sushil K. Sarna. Impairment of Ca21 mobilization in circular muscle cells of the inflamed colon. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G234– G242, 2000.—This study investigated whether inflammation modulates the mobilization of Ca21 in canine colonic circular muscle cells. The contractile response of single cells from the inflamed colon was significantly suppressed in response to ACh, KCl, and BAY K8644. Methoxyverapamil and reduction in extracellular Ca21 concentration dose-dependently blocked the response in both normal and inflamed cells. The increase in intracellular Ca21 concentration in response to ACh and KCl was significantly reduced in the inflamed cells. However, Ca21 efflux from the ryanodineand inositol 1,4,5-trisphosphate (IP3)-sensitive stores, as well as the decrease of cell length in response to ryanodine and IP3, were not affected. Heparin significantly blocked Ca21 efflux and contraction in response to ACh in both conditions. ACh-stimulated accumulation of IP3 and the binding of [3H]ryanodine to its receptors were not altered by inflammation. Ruthenium red partially inhibited the response to ACh in normal and inflamed states. We conclude that the canine colonic circular muscle cells utilize Ca21 influx through L-type channels as well as Ca21 release from the ryanodineand IP3-sensitive stores to contract. Inflammation impairs Ca21 influx through L-type channels, but it may not affect intracellular Ca21 release. The impairment of Ca21 influx may contribute to the suppression of circular muscle contractility in the inflamed state.