title: Propagation of pacemaker activity in the guinea-pig antrum.
abstract: 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 degrees 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 (Delta 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 interstitial cells of Cajal, ICC-IM, and smooth muscle cells, and the local distortion (contraction) in a field of view. TTX (1 microm) had little effect on slow wave or pacemaker potential activity, but 2-APB (50 microm) blocked all Ca(2+) waves, indicating a pivotal role for intracellular Ca(2+) stores. Nicardipine (2 microm) 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.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Hennig
authors.forename: G D S
authors.initials: GD
authors.lastname: Hirst
authors.forename: K J
authors.initials: KJ
authors.lastname: Park
authors.forename: C B
authors.initials: CB
authors.lastname: Smith
authors.forename: K M
authors.initials: KM
authors.lastname: Sanders
authors.forename: S M
authors.initials: SM
authors.lastname: Ward
authors.forename: T K
authors.initials: TK
authors.lastname: Smith
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011706:Pyloric Antrum / Q000166:cytology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D013779:Tetrodotoxin; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium