Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Abstract

1 The rat colonic circular muscle displays cyclic episodes of myenteric potential oscillations (MPOs), each of them associated with a spontaneous contraction. Nifedipine 1 mM abolished both MPOs and their associated contractions. TTX (1 mM) increased the amplitude and frequency of spontaneous contractions. 2 Electrical ®eld stimulation (EFS) induced a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an initial fast hyperpolarization (characterized by IJP amplitude) and a sustained hyperpolarization (characterized by IJP duration). 3 Sodium nitroprusside (10 mM) hyperpolarized and abolished spontaneous contractions even in presence of TTX or 1 mM apamin. ATP (100 mM) also hyperpolarized and abolished spontaneous contractions but its e ects were decreased by TTX and abolished by apamin. 4 Suramin (100 mM) or apamin reduced the amplitude of the IJPs, but did not a ect their duration. Incubation with L-NOARG (1 mM) reduced the duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but a residual IJP could still be recorded. 5 We conclude that the mechanical and electrical cyclic activity of the rat colonic circular muscle is modulated but not originated by the enteric nervous system and involves L-type calcium channel activity. EFS induces release of NANC inhibitory neurotransmitters which hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP generation: ATP is responsible for the ®rst phase of the IJPs involving activation of apamin-sensitive potassium channels, whereas NO initiates the second phase which is independent of the activation of such channels.

Participation of ATP in Nonadrenergic, Noncholinergic Relaxation of Longitudinal Muscle of Wistar Rat Jejunum

“…ATP has been suggested to mediate apamin-sensitive fast i.j.ps in various intestinal regions of several animal species (9,13,14,31). In the present study, apamin completely inhibited i.j.ps induced by two pulses of EFS at 20 Hz (this stimulation gave the most reproducible responses).…”

“…On the other hand, exogenous ATPinduced relaxation was shown to be apamin-sensitive (2). EFS-induced fast inhibitory junction potentials (i.j.ps) were suggested to be mediated by ATP and to be apamin-sensitive in the circular muscle of the human jejunum (11), the guinea pig ileum (12), the rat colon (13), the guinea pig colon (14), and the mouse distal colon (15). Although these results suggest a role of ATP in NANC relaxation, several reports present contradictory results: no role for ATP was suggested in the rat ileum (16), proximal colon (17), and caecum (18) and the guinea pig gastric fundus (19).…”

Purinergic and nitrergic junction potential in the human colon

“…In contrast, in other species, short pulses cause a biphasic IJP with a fast component followed by a sustained one (9,18,27). Usually, the fast component is L-NNA insensitive, and the sustained component is L-NNA sensitive, showing that NO and a second neurotransmitter are involved in the inhibitory response.…”

Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract

“…Pharmacological experiments revealed the first component to be dependent on activation of small-conductance, Ca 2ϩ -activated K ϩ channels and to be induced by purines (2,10,21,35). The second component is blocked by inhibitors of nitric oxide synthase (NOS) and is therefore regarded as nitrergic (5,23,31). This characteristic biphasic IJP has been shown for several other regions of the GI tract of different species as well, such as antrum (15), small intestine (12), and internal anal sphincter (6,30).…”