1. The effects of the phosphodiesterase inhibitors caffeine, theophylline, isobutylmethylxanthine (IBMX) and rolipram on spontaneous electrical activity (slow waves) were studied in the circular muscle of the guinea‐pig gastric antrum. 2. All the inhibitors reduced slow wave frequency without changing the membrane potential and the slow wave configuration, but at higher concentrations they blocked the slow waves and caused membrane hyperpolarization. In the presence of the inhibitors a low level of irregular electrical activity could be observed in many preparations. 3. Isoprenaline, forskolin, dibutyryl cAMP and 8‐bromo‐cAMP all produced effects essentially similar to those of phosphodiesterase inhibitors. K+ (12 mM) and removal of K+ both depolarized the membrane and these were not affected by IBMX (1‐3 microM). A decrease in frequency caused by IBMX was also not significantly affected by 12 mM K+ or K+ removal and only partially antagonized by TEA or 4‐aminopyridine. 4. These results suggest that an increase in intracellular cAMP inhibits pacemaker activity of slow waves. An increase in K+ conductance does not seem to be a major factor in this inhibition. Slow waves appear to be a compound electrical activity in a group of muscle cells and are likely to be disintegrated by xanthine derivatives.

At the boundary between the proximal and distal divisions of the colon in the guinea-pig is a ring-like section which rhythmically contracts. HUKUHARA and his co-researchers demonstrated that antiperistaltic movements in the proximal colon start from this ring-like section, the so-called pacemaker area. Tissue specimens, 0.1-0.3 mm in width/height x 4-7 mm in length, were prepared from various parts of this area. Significantly, in the circular muscle at the mesenteric border, a nodular structure spontaneously producing 10-12 cycle/min regular mechanical contractions was found. Moreover, histological investigations after physiological recording revealed that the presence of the inner-most and/or outermost portions of the circular muscle coat was not necessary for these spontaneous activities. Champy-Maillet (ZIO) staining showed that smooth muscle cells in this spontaneously contracting nodule were heavily innervated. Transmission electron microscopy showed that the smooth muscle tissue of this particular area was characterized by scanty interstitial elements such as fibroblasts. Plasma membranes of adjacent smooth muscle cells were frequently in direct contact with each other, forming many gap junctions. Scanning electron microscopy in the specimen prepared using a NaOH-maceration method revealed fine three-dimensional relationships between nerve terminals and smooth muscle cells. The nodular structure described in this paper may provide a useful experimental model for the investigation of colonic motility and its neural control.

No abstract

Antiperistalses occur from the flexure region of the guinea pig colon. We previously demonstrated that the circular muscle at the mesenteric border of the flexure region produced spontaneous regular contractions and found special smooth muscle cells believed to be pacemakers along the submucosal surface of the circular muscle layer. In this study, we revealed bipolar- and multipolar-type special smooth muscle cells along the submucosal surface of the muscle layer. Their slender cell processes contacted each other and formed a cellular network. Caveolae, filament structures expressing smooth muscle actin, vimentin, some desmin, and basal lamina were prominent features. The special smooth muscle cells corresponded to c-Kit-immunopositive cells and so-called interstitial cells or interstitial cells of Cajal in other reports. Their population was larger in the flexure region and the proximal colon than in the distal colon. The circular muscle layer at the flexure region was thicker than in other regions. The contraction in the flexure region showed the highest frequency and regularity. The dense population of special smooth muscle cells at the flexure region and thicker muscle layer may make the mechanical contraction more regular. The antiperistalsis from the flexure region could be explained in relation to the highest frequency of the pulsating contraction.

Effects of cyanide (CN) on spontaneous mechanical and electrical activities were studied in the circular muscle of the guinea-pig gastric antrum. CN (0.05-0.5 mM) inhibited both mechanical and electrical activities, but the inhibition was stronger in the former than the latter (slow wave). When glucose was removed for more than 30 min, slow wave was also blocked by CN. It is likely that ATP necessary for the generation of spontaneous activity can be supplied through either glycolysis or oxidative phosphorylation. CN slightly depolarized the membrane and the inhibition by CN was not affected by glibenclamide, a blocking agent of ATP-regulated K+ channel, suggesting that this channel is not activated by CN treatment. Basal level of intracellular Ca2+ measured with fura-2 tended to increase during the mechanical inhibition by CN. This was also clearly demonstrated in excess (60 mM) K+ solution. These results suggest that intracellular Ca2+ regulation is impaired and that there is uncoupling between intracellular Ca2+ and tension development in the presence of CN.