Induction and organization of Ca2+ waves by enteric neural reflexes

The motility of the gastrointestinal tract consists of local, nonpropulsive mixing (pendular or segmental) and propulsive (peristaltic) movements(1-5) . It is generally considered that mixing movements are produced by intrinsi c pacemakers which generate rhythmic contractions(4-6), and peristalsis by intrinsic excitatory and inhibitory neural reflex pathways(1-5,7,8), but th e relationship between mixing and peristalsis is poorly understood4-6. Peri stalsis is compromised in mice lacking interstitial cells of Cajal(9), sugg esting that these pacemaker cells(10-14) may also be involved in neural ref lexes. Here we show that mixing movements within longitudinal muscle result from spontaneously generated waves of elevated internal calcium concentrat ion which originate from discrete locations (pacing sites), spread with ani sotropic conduction velocities in all directions, and terminate by collidin g with each other or with adjacent neurally suppressed regions. Excitatory neural reflexes control the spread of excitability by inducing new pacing s ites and enhancing the overall frequency of pacing, whereas inhibitory refl exes suppress the ability of calcium waves to propagate. We provide evidenc e that the enteric nervous system organizes mixing movements to generate pe ristalsis, linking the neural regulation of pacemakers to both types of gut motility.