Enteric sensory neurons communicate with interstitial cells of Cajal to affect pacemaker activity in the small intestine

Abstract

Enteric sensory neurons (the AH neurons) play a role in control of gastrointestinal motor activity; AH neuron activation has been proposed to change propulsion into segmentation. We sought to find a mechanism underlying this phenomenon. We formulated the hypothesis that AH neurons increase local ICC-MP (interstitial cells of Cajal associated with the myenteric plexus) pacemaker frequency to disrupt peristalsis and promote absorption. To that end, we sought structural and physiological evidence for communication between ICC-MP and AH neurons. We designed experiments that allowed us to simultaneously activate AH neurons and observe changes in ICC calcium transients that underlie its pacemaker activity. Neurobiotin injection in AH neurons together with ICC immunohistochemistry proved the presence of multiple contacts between AH neuron varicosities and the cell bodies and processes of ICC-MP. Generating action potential activity in AH neurons led to increase in the frequency and amplitude of calcium transients underlying pacemaker activity in ICC. When no rhythmicity was seen, rhythmic calcium transients were evoked in ICC. As a control, we stimulated nitrergic S neurons, which led to reduction in ICC calcium transients. Hence, we report here the first demonstration of communication between AH neurons and ICC. The following hypothesis can now be formulated: AH neuron activation can disrupt peristalsis directed by ICC-MP slow wave activity, through initiation of a local pacemaker by increasing ICC pacemaker frequency through increasing the frequency of ICC calcium transients. Evoking new pacemakers distal to the proximal lead pacemaker will initiate both retrograde and antegrade propulsion causing back and forth movements that may disrupt peristalsis.

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators

“…; Zhu et al . , ). In physiological conditions, a stimulus is most likely to be experienced locally and not to be uniform along the entire intestine.…”

Haustral boundary contractions in the proximal 3-taeniated rabbit colon

“…The gap junction contacts between ICC and smooth muscle cells make the ICC ideal to convey important information from the nerves to smooth muscle cells. Even in ICC with stimulus-independent slow-wave activity, the enteric nerves can modulate the pacemaker frequency (22,64). Hence, if the haustral boundary contractions have an ICC network as the origin of their rhythmicity, and if this pacemaker activity is dependent on neural excitation of the ICC, then the pacemaker activity will be abolished by TTX.…”

The role of telocytes in morphogenetic bioelectrical signaling: once more unto the breach

“…They are reported as being capable of spontaneously initiating electrical activity, which can be modulated by the stimulation of enteric nerves (Zhu et al, 2013); this process involves calcium transients (Yamashita, 2010). Cretoiu et al (2013) reported the existence of hyperpolarization-activated chloride-inward current with calcium dependence and the absence of L-type calcium channels in human myometrium.…”