Submitted on November 5, 2007
Accepted on June 30, 2008
Purinergic and nitrergic junction potential in the human colon
Diana Gallego1, Victor Gil2, Jordi Aleu2, Mariona Auli3, Pere Clave4, and Marcel Jimenez1*
1 Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
2 Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
3 Fundacio de Gastroenterologia Dr Vilardell and Department of Surgery, Hospital de Mataro, Mataro, Spain
4 Fundacio de Gastroenterologia Dr Vilardell and Department of Surgery, Hospital de Mataro, Mataro, Barcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: marcel.jimenez{at}uab.es.
The aim of the present work is to investigate a putative junction transmission (nitric oxide [NO] and ATP) in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. Results: 1- The NO donor NaNP (10µM) but not the P2Y receptor agonist ADP
S (10µM) was able to cause a sustained relaxation. 2- L-NNA (1mM) a nitric oxide synthase inhibitor, but not MRS2179 (10µM) a P2Y1 antagonist increased spontaneous motility. 3- Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS2179 (10µM). 4- EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5Hz. 5- Two consecutive single pulses induced MRS2179-sensitive fIJPs that showed a rundown. 6- The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1mM), Hexamethonium (100µM), MRS2179 (1µM) and NF023 (10µM). We conclude 1- single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; 2- NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).
