Pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2007-06, Vol.292 (6), p.G1499-G1510
• Main Authors: Albertí, E, Mikkelsen, H B, Wang, X Y, Díaz, M, Larsen, J O, Huizinga, J D, Jiménez, M
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Apamin - pharmacology; Biological Clocks - drug effects; Colon; Colon - cytology; Colon - drug effects; Colon - innervation; Colon - metabolism; Electric Stimulation; Enzyme Inhibitors - pharmacology; Gastrointestinal Motility - drug effects; In Vitro Techniques; Male; Motor Neurons - metabolism; Muscle Contraction; Muscle Relaxation; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - metabolism; Muscular system; Mutation; Myenteric Plexus - cytology; Myenteric Plexus - metabolism; Neural Inhibition - drug effects; Neuromuscular Junction - drug effects; Neuromuscular Junction - metabolism; Neurotransmitters; Nitrergic Neurons - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitroarginine - pharmacology; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Rats; Rats, Mutant Strains; Rodents; Sodium Channel Blockers - pharmacology; Tetrodotoxin - pharmacology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00136.2006

The aim of this study was to characterize the pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats, which harbor a mutation in the c-kit gene that affects development of interstitial cells of Cajal (ICC). In Ws/Ws rats, the density of KIT-positive cells was markedly reduced. Wild-type, but not Ws/Ws, rats showed low- and high-frequency cyclic depolarization that were associated with highly regular myogenic motor patterns at the same frequencies. In Ws/Ws rats, irregular patterns of action potentials triggered irregular muscle contractions occurring within a bandwidth of 10-20 cycles/min. Spontaneous activity of nitrergic nerves caused sustained inhibition of muscle activity in both wild-type (+/+) and Ws/Ws rats. Electrical field stimulation of enteric nerves, after blockade of cholinergic and adrenergic activity, elicited inhibition of mechanical activity and biphasic inhibitory junction potentials both in wild-type and Ws/Ws rats. Apamin-sensitive, likely purinergic, inhibitory innervation was not affected by loss of ICC. Variable presence of nitrergic innervation likely reflects the presence of direct nitrergic innervation to smooth muscle cells as well as indirect innervation via ICC. In summary, loss of ICC markedly affects pacemaker and motor activities of the rat colon. Inhibitory innervation is largely maintained but nitrergic innervation is reduced possibly related to the loss of ICC-mediated relaxation.