Effect of purified Clostridium difficile toxins on intestinal smooth muscle. I. Toxin A.
In these studies we determined the effects of purified Clostridium difficile toxin A, an enterotoxin, on the electrophysiological and contractile properties of rabbit intestinal circular smooth muscle and correlated these effects with changes of smooth muscle morphology. Simultaneous measurements of intracellular membrane potential and contractility were determined in excised ileal muscle strips after administration of toxin A in vivo (60 micrograms/ml) into an isolated rabbit ileal loop or directly in vitro (0.1-60 micrograms/ml) to a normal muscle strip. Toxin A injection in vivo resulted in membrane depolarization and increased slow wave and action potential frequency. Toxin A injection in vivo also caused increased amplitude of spontaneous and carbachol-induced phasic contractions. The electrophysiological effects of in vivo administration of toxin A were correlated with an inflammatory infiltrate of the lamina propria, but no light or electron microscopic evidence of injury to smooth muscle cells was seen. In contrast to the in vivo studies, direct in vitro exposure of normal ileal muscle strips to toxin A had no effect on either spontaneous or carbachol-induced electromechanical activity. Our results indicate that in vivo administration of C. difficile toxin A into a rabbit ileal loop, but not direct in vitro exposure, causes significant alterations of smooth muscle excitation-contraction coupling that may be mediated by products of local inflammatory cells.