Submitted on January 23, 2009
Revised on June 12, 2009
Accepted on June 23, 2009
Slow synaptic transmission in myenteric AH neurons from the inflamed guinea-pig ileum
Kulmira Nurgali1*, Trung V Nguyen2, Michelle Thacker1, Louise Pontell1, and John B Furness3
1 The University of Melbourne
2 University of Melbourne
3 UIniversity of Melbourne
* To whom correspondence should be addressed. E-mail: k.nurgali{at}unimelb.edu.au.
We investigated the effect of inflammation on slow synaptic transmission in myenteric neurons in the guinea-pig ileum. Inflammation was induced by the intraluminal injection of trinitrobenzene sulphonate and tissues were taken for in vitro investigation 6-7 days later. Brief tetanic stimulation of synaptic inputs (20Hz, 1s) induced slow excitatory postsynaptic potentials (EPSPs) in 49% and maintained postsynaptic excitation that lasted from 27 min to 3 hours in 13% of neurons from the inflamed ileum. These neurons were classified electrophysiologically as AH neurons: 10 were morphological type II neurons and one was type I. Such long-term hyperexcitability after a brief stimulus is not encountered in enteric neurons of normal intestine. Electrophysiological properties of neurons with maintained postsynaptic excitation were similar to those of neurons with slow EPSPs. Another form of prolonged excitation, sustained slow postsynaptic excitation (SSPE), induced by 1Hz, 4min stimulation, in type II neurons from the inflamed ileum reached its peak earlier, but had lower amplitude that in control. Unlike slow EPSPs, and similar to SSPEs, maintained excitation was not inhibited by NK1 or NK3 receptor antagonists. Maintained postsynaptic excitation was not influenced by PKC inhibitors, but the PKA inhibitor, H-89, caused further increase in neuronal excitability. In conclusion, maintained excitation, observed only in neurons from the inflamed ileum, may contribute to the dysmotility, pain and discomfort associated with intestinal inflammation.
