Experiments are proposed to study the basic electrophysiology of canine pyloric sphincter. The electrical activity of the pylorus is complicated and has not been adequately described by previous extracellular recordings or by the few reported intracellular studies. We have developed cross-sectional preparations of the pyloric muscularis which allow precise placement of intracellular microelectrodes to characterize the electrical activity at any point within the pyloric ring or at any level through the thickness of the muscle. A complete analysis of pyloric electrical waveforms will be performed. Preliminary studies have revealed that pyloric muscles are paced by antral electrical activity and that much of the pylorus may be quiescent when it is uncoupled from the distal antrum. We have also observed that slow waves decay in amplitude as they propogate through the circular layer or distally through the pyloric ring. The bulk of the circular muscle of the pylorus appears to be a passive syncytium which does not generate or regenerate slow wave activity. This raises the question of how the pylorus is activated, and how its activity is coordinated with gastric peristaltic activity. Experiments to answer these questions will be performed. The origin and mechanisms of propagation of electrical events will be determined. We will also investigate regulation of electrical activity within the pylorus, specifically how neurotransmitters and hormonal influences affect spontaneous events and the propagation of electrical events. An initial hypothesis is that neural regulation controls the frequency of activity at the pacemaker sites more proximal to the pylorus, but the amplitude of electrical events and the extent of the spread of these events into the pyloric ring depends upon neural and hormonal conditioning of the syncytial cable properties and excitability mechanisms. We will also determine the relationship between electrical and mechanical events. Finally we will attempt to correlate electrophysiological characteristics with structural measurements. We hope to reconcile electrical responses to neural stimulation with measurements of innervation density and cable parameters to structural characteristics of the syncytium. These experiments should provide a basis for understanding the basic mechanisms controlling pyloric motility and help to explain the role of the pylorus in regulating gastric emptying.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040569-04
Application #
3240922
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1988-08-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Nevada Reno
Department
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
Sanders, Kenton M; Hennig, Grant (2015) Measuring Gastrointestinal Electrical Activity With Extracellular Electrodes: Author's Reply. J Neurogastroenterol Motil 21:625-6
Sanders, Kenton M; Zhu, Mei Hong; Britton, Fiona et al. (2012) Anoctamins and gastrointestinal smooth muscle excitability. Exp Physiol 97:200-6
Bayguinov, O; Hennig, G W; Sanders, K M (2011) Movement based artifacts may contaminate extracellular electrical recordings from GI muscles. Neurogastroenterol Motil 23:1029-42, e498
Rhee, Poong-Lyul; Lee, Ji Yeon; Son, Hee Jung et al. (2011) Analysis of pacemaker activity in the human stomach. J Physiol 589:6105-18
Sanders, Kenton M; Hwang, Sung Jin; Ward, Sean M (2010) Neuroeffector apparatus in gastrointestinal smooth muscle organs. J Physiol 588:4621-39
Zhu, Mei Hong; Kim, Tae Wan; Ro, Seungil et al. (2009) A Ca(2+)-activated Cl(-) conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J Physiol 587:4905-18
Hwang, Sung Jin; Blair, Peter J A; Britton, Fiona C et al. (2009) Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol 587:4887-904
McCloskey, K D; Anderson, U A; Davidson, R A et al. (2009) Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice. Br J Pharmacol 156:273-83
Faville, R A; Pullan, A J; Sanders, K M et al. (2008) A biophysically based mathematical model of unitary potential activity in interstitial cells of Cajal. Biophys J 95:88-104
Takeda, Yukari; Koh, Sang Don; Sanders, Kenton M et al. (2008) Differential expression of ionic conductances in interstitial cells of Cajal in the murine gastric antrum. J Physiol 586:859-73

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