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 s ingle cells from the inflamed colon was significantly suppressed in respons e to ACh, KCl, and BAY K8644. Methoxyverapamil and reduction in extracellul ar Ca2+ concentration dose-dependently blocked the response in both normal and inflamed cells. The increase in intracellular Ca2+ concentration in res ponse to ACh and KCl was significantly reduced in the inflamed cells. Howev er, 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 rya nodine and IP3, were not affected. Heparin significantly blocked Ca2+ emux and contraction in response to ACh in both conditions. ACh-stimulated accum ulation of IP3 and the binding of [H-3]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 circ ular muscle cells utilize Ca2+ influx through L-type channels as well as Ca 2+ release from the ryanodine- and IP3-sensitive stores to contract. Inflam mation impairs Ca2+ influx through L-type channels, but it may not affect i ntracellular Ca2+ release. The impairment of Ca2+ influx may contribute to the suppression of circular muscle contractility in the inflamed stale.