THE ROLE OF LARGE CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS TO GASTROINTESTINAL MOTILITY

Abstract

Aim: This study is designed to investigate the role of large conductance calciumactivated (BK) channels in regulating gastrointestinal motility using mouse ileum strips
in an organ bath preparation.
Place and duration of study: This study was conducted in the School of Pharmacy
and Biomedical Science at the University of Portsmouth, UK for a period of four
months, from September 2015 to January 2016
Methodology: Experimental procedures to test viability of mouse ileum and response
to compound NS19504 and Tetraethyl ammonium (TEA) were conducted using organ
bath preparation containing Krebs solution. Force of contraction and relaxation of each
ileum section were measured and recorded using Labchart reader. Paired t-test
conducted using GraphPad prism software for statistical analysis of results.
Results: Carbachol generated a concentration-dependent contraction in the tissue strip
and NS19504 relaxed the tissue. TEA used as a large-conductance calcium-activated
(BK) channel blocker raised the amplitude of contraction after Carbachol, and had no
effect on relaxation generated by NS19504. Unpaired t-test produced a p-value <0.0001
(<0.05) meaning there is a significant difference between amplitude of contraction in
the presence and absence of TEA. Mean ± SEM in the presence of TEA = 0.205±0.02,
mean ± SEM in the absence of TEA= 0.05±0.01 (N=6)
Conclusion: Results from this study suggest that administration of NS19504 produced
concentration dependent relaxation of the tissue and this relaxation is not blocked by
TEA, which is a known BK channel blocker. Better understanding of the pathological
roles played by ion channels may be useful in the development of more potent drugs
targeting ion channels to treat gastrointestinal (GI) motility disorders.