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Propagation of pacemaker activity in the guinea-pig antrum

Cyclical periods of depolarization (slow waves) underlie peristaltic contractions involved in mixing and emptying of contents in the gastric antrum. Slow waves originate from a myenteric network of interstitial cells of Cajal (ICC-MY). In this study we have visualized the sequence and propagation of...

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Published in:The Journal of physiology 2004-04, Vol.556 (2), p.585-599
Main Authors: Hennig, G. W., Hirst, G. D. S., Park, K. J., Smith, C. B., Sanders, K. M., Ward, S. M., Smith, T. K.
Format: Article
Language:English
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Summary:Cyclical periods of depolarization (slow waves) underlie peristaltic contractions involved in mixing and emptying of contents in the gastric antrum. Slow waves originate from a myenteric network of interstitial cells of Cajal (ICC-MY). In this study we have visualized the sequence and propagation of Ca 2+ transients associated with pacemaker potentials in the ICC network and longitudinal (LM) and circular muscle (CM) layers of the isolated guinea-pig gastric antrum. Gastric antrum was dissected to reveal the ICC-MY network, loaded with Fluo-4 AM and activity was monitored at 37°C. Ca 2+ waves propagated throughout the ICC-MY network at an average velocity of 3.24 ± 0.12 mm s −1 at a frequency of 4.87 ± 0.16 cycles min −1 ( n = 4). The propagation of the Ca 2+ wave often appeared ‘step-like’, with separate regions of the network being activated after variable delays. The direction of propagation was highly variable (Δ angle of propagation 44.3 ± 10.9 deg per cycle) and was not confined to the axes of the longitudinal or circular muscle. Ca 2+ waves appeared to spread out radially from the site of initiation. The initiating Ca 2+ wave in ICC-MY was correlated to secondary Ca 2+ waves in intramuscular interstial cells of Cajal, ICC-IM, and smooth muscle cells, and the local distortion (contraction) in a field of view. TTX (1 μ m ) had little effect on slow wave or pacemaker potential activity, but 2-APB (50 μ m ) blocked all Ca 2+ waves, indicating a pivotal role for intracellular Ca 2+ stores. Nicardipine (2 μ m ) eliminated the Ca 2+ transient generated by smooth muscle, but did not affect the fast upstroke associated with ICC-MY. These results indicate that slow waves follow a sequence of activation, beginning with the ICC-MY and ICC-IM network, followed later by a sustained Ca 2+ transient in the muscle layers that is responsible for contraction.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2003.059055