TY - JOUR
T1 - Pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats
AU - Albertí, Elena
AU - Mikkelsen, Hanne Birte
AU - Wang, Xuanyu
AU - Díaz, Mario
AU - Larsen, Jytte Overgaard
AU - Huizinga, J D
AU - Jiménez, Marcel
N1 - Keywords: Action Potentials; Animals; Apamin; Biological Clocks; Colon; Electric Stimulation; Enzyme Inhibitors; Gastrointestinal Motility; Male; Motor Neurons; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Mutation; Myenteric Plexus; Neural Inhibition; Neuromuscular Junction; Nitrergic Neurons; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Proto-Oncogene Proteins c-kit; Rats; Rats, Mutant Strains; Sodium Channel Blockers; Tetrodotoxin
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1152/ajpgi.00136.2006
DO - 10.1152/ajpgi.00136.2006
M3 - Journal article
C2 - 17322067
SN - 0193-1857
VL - 292
SP - G1499-510
JO - American Journal of Physiology: Gastrointestinal and Liver Physiology
JF - American Journal of Physiology: Gastrointestinal and Liver Physiology
IS - 6
ER -