Impairment of Ca²⁺ mobilization in circular muscle cells of the inflamed colon

This study investigated whether inflammation modulates the mobilization of Ca²⁺ 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 Ca²⁺ concentration dose-dependently blocked the response in both normal and inflamed cells. The increase in intracellular Ca²⁺ concentration in response to ACh and KCl was significantly reduced in the inflamed cells. However, Ca²⁺ efflux from the ryanodine- and 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 Ca²⁺ 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 Ca²⁺ influx through L-type channels as well as Ca²⁺ release from the ryanodine- and IP₃-sensitive stores to contract. Inflammation impairs Ca²⁺ influx through L-type channels, but it may not affect intracellular Ca²⁺ release. The impairment of Ca²⁺ influx may contribute to the suppression of circular muscle contractility in the inflamed state.