title: Dynamics of inhibitory co-transmission, membrane  potential and pacemaker activity determine neuromyogenic  function in the rat colon.
abstract: Interaction of different neuromyogenic mechanisms determines colonic motility. In rats, cyclic depolarizations and slow waves generate myogenic contractions of low frequency (LF) and high frequency (HF), respectively. Interstitial cells of Cajal (ICC) located near the submuscular plexus (SMP) generate slow waves. Inhibitory junction potential (IJP) consists on a purinergic fast (IJPf) followed by a nitrergic slow (IJPs) component leading to relaxation. In the present study, we characterized (1) the dynamics of purinergic-nitrergic inhibitory co-transmission and (2) its contribution on prolonged inhibition of myogenic activity. Different protocols of electrical field stimulation (EFS) under different pharmacological conditions were performed to characterize electrophysiological and mechanical responses. Smooth muscle cells (SMCs) in tissue devoid of ICC-SMP had a resting membrane potential (RMP) of -40.7 ± 0.7 mV. Single pulse protocols increased purinergic and nitrergic IJP amplitude in a voltage-dependent manner (IJPfMAX = -26.4 ± 0.6 mV, IJPsMAX = -6.7 ± 0.3 mV). Trains at increasing frequencies enhanced nitrergic (k = 0.8 ± 0.2 s, IJPs∞ = -15 ± 0.5 mV) whereas they attenuated purinergic responses (k = 3.4 ± 0.6 s,IJPf∞ = -8.9 ± 0.6 mV). In tissues with intact ICC-SMP, the RMP was -50.0 ± 0.9 mV and nifedipine insensitive slow waves (10.1 ± 2.0 mV, 10.3 ± 0.5 cpm) were recorded. In these cells, (1) nitrergic and purinergic responses were reduced and (2) slow waves maintained their intrinsic frequency and increased their amplitude under nerve-mediated hyperpolarization. Based on the co-transmission process and consistent with the expected results on RMP, prolonged EFS caused a progressive reduction of LF contractions whereas HF contractions were partially insensitive. In conclusion, inhibitory neurons modulate colonic spontaneous motility and the principles determining post-junctional responses are (1) the frequency of firing that determines the neurotransmitter/receptor involved, (2) the transwall gradient and (3) the origin and nature of each myogenic activity
authors.forename: Noemí
authors.initials: N
authors.lastname: Mañé
authors.forename: Víctor
authors.initials: V
authors.lastname: Gil
authors.forename: Míriam
authors.initials: M
authors.lastname: Martínez-Cutillas
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Martín
authors.forename: Diana
authors.initials: D
authors.lastname: Gallego
authors.forename: Marcel
authors.initials: M
authors.lastname: Jiménez
mesh_terms: D000200:Action Potentials; D000818:Animals; D003106:Colon / Q000166:cytology / Q000502:physiology*; D005769:Gastrointestinal Motility; D056885:Interstitial Cells of Cajal / Q000502:physiology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010507:Periodicity; D058913:Purinergic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058913:Purinergic Agonists; D019001:Nitric Oxide Synthase