Effects of Nifedipine and Nickel on Plateau Potentials Generated in Submucosal Interstitial Cells Distributed in the Mouse Proximal Colon.

Abstract

The effects of nifedipine and nickel ions (Ni 2+ ), known inhibitors of L-and T-type voltage-gated Ca-channels respectively, were investigated on plateau potentials recorded from submucosal interstitial cells distributed in the mouse proximal colon. Plateau potentials were generated at a frequency of about 15 times min -1 and were formed of two components. The primary component had an initial fast rate of rise with a transient potential (rate of rise, 130 mV/s; peak amplitude, 35 mV) and was followed by a secondary plateau component with a sustained potential (amplitude, 25 mV; duration, 2.6 s). Each cell from which recordings were made was injected with neurobiotin. Subsequent morphological examination with a confocal microscope indicated successful visualization of injected cells only in the presence of 18β-glycylrhetinic acid (an inhibitor of gap junctional connections), suggesting that these cells were dye-coupled with surrounding cells. The cells injected with neurobiotin exhibited an oval-shaped cell body with bipolar processes and were distributed in the submucosal layer, suggesting that they were submucosal interstitial cells of Cajal (ICC-SM). The plateau potentials were not altered by 0.01 µM nifedipine, but were reduced in duration by 0.1 µM nifedipine, and abolished by 1 µM nifedipine. The rate of rise of plateau potentials, but not their amplitude, was reduced by Ni 2+ (> 10 µM), with no significant alteration of the membrane potential. In the presence of 100 µM Ni 2+ , the plateau potentials were changed to a triangular form. Thus, the plateau potentials were formed by two types of voltage-gated channel current: the initial component was produced by a Ni 2+ -sensitive channel current and the plateau component by a nifedipine-sensitive current. The possible involvement of two different types of voltage-gated Ca 2+ -channels in the generation of submucosal pacemaker potentials was discussed.

Motility patterns and distribution of interstitial cells of Cajal and nitrergic neurons in the proximal, mid‐ and distal‐colon of the rat

“…This is consistent with the hypothesis that the pacemaker responsible for HF contractions is the ICC network located at the submucosal border. Moreover, it has been recently reported that in the mouse colon near the submucosa, c‐kit positive cells generate ‘plateau potentials’ at a frequency of about 15 min −1 27,33 . These plateau potentials are very similar in frequency to the slow wave activity previously described in the rat colon 24 and are responsible for HF contractions described all along the colon in the present work.…”

Properties of acetylcholine-induced relaxation of smooth muscle isolated from the proximal colon of the guinea-pig

“…We, therefore, would like to propose that in the proximal colon of the guinea-pig, there is a population of nitrergic nerves whose cell bodies are located in the submucosal layer, that receive cholinergic inputs and which send axons to circular smooth muscle cells. The proximal colon is rich in ICC-SMP (Kobayashi et al, 1995;Kobayashi et al, 1996;Nahar et al, 1998;Pluja et al, 2001), and these cells periodically generate plateau-type action potentials (Yoneda et al, 2002;Yoneda et al, 2003;Hotta et al, 2005). While the physiological functions of ICC-SMP remain unclear, we consider that their activity is possibly involved in the special digestive movements found in the proximal colon, such as in anti-peristaltic movements (Hukuhara and Neya, 1968).…”

Properties of spontaneous contractions and their modulation by transmural nerve stimulation in circular smooth muscle isolated from the pacemaker area in the flexure region of the guinea-pig colon

“…These results suggest that the activity of the ICC-MP is independent of that of the ICC-SMP. In the mouse, ICC-SMP produce plateau-type action potentials which are conducted to circular smooth muscle cells, possibly in an electrotonic manner, to elicit action potentials (Yoneda et al, 2002;Yoneda et al, 2003;Hotta et al, 2007). It was therefore considered that the activity propagated from one type of ICC could not be conducted to other types of ICC, or alternatively the activity propagated from one type of ICC was insufficient to modulate the activity of other types of ICC.…”