L-type Ca2+ channels in the enteric nervous system mediate oscillatory Cl- secretion in guinea pig colon

Mariko Nishikitani, Yukiko Yasuoka, Hideaki Kawada, Katsumasa Kawahara

Research output: Contribution to journalArticle

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Abstract

The enteric nervous system regulates epithelial ion and fluid secretion. Our previous study has shown that the low (0.2-1 mM) concentrations of Ba2+, a K+ channel inhibitor, evoke Ca2+ -dependent oscillatory Cl- secretion via activation of submucosal cholinergic neurons in guinea pig distal colon. However, it is still unclear which types of Ca2+ channels are involved in the oscillation at the neuro-epithelial junction. We investigated the inhibitory effects of organic and inorganic Ca2+, channel antagonists on the short circuit current (Isc) of colonic epithelia (mucosa-submucosa sheets) mounted in Ussing chambers. The amplitude (412 ± 37 μA cm-2) and frequency (2.6 ± 0.1 cycles min-1) of the Ba2+ -induced Isc in normal (1.8 mM) Ca2+ solution (n = 26) significantly decreased by 37.6% and 38.5%, respectively, in the low (0.1 mM) Ca2+ solution (n = 14). The Isc amplitude was reversibly inhibited by either verapamil (an L-type Ca2+ channel antagonist) or divalent cations (Cd2+, Mn2+, Ni2+) in a concentration-dependent manner. The concentration of verapamil for half-maximum inhibition (IC50) was 4 and 2 μM in normal and low Ca2+ solution, respectively. The relative blocking potencies of metal ions were Cd2+ > Mn2+, Ni2+ in normal Ca2+ solution. In contrast, the frequency of Isc,, was unchanged over the range of concentrations of the Ca2+ channel antagonists used. Our results show that the oscillatory Isc evoked by Ba2+ involves L-type voltage-gated Ca2+ channels. We conclude that L-type Ca2+ channels play a key role in the oscillation at the neuroepithelial junctions of guinea pig colon.

Original languageEnglish
Pages (from-to)151-160
Number of pages10
JournalTohoku Journal of Experimental Medicine
Volume211
Issue number2
DOIs
Publication statusPublished - Feb 8 2007
Externally publishedYes

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Enteric Nervous System
Neurology
Guinea Pigs
Colon
Verapamil
Ions
Fluids and Secretions
Cholinergic Neurons
Divalent Cations
Short circuit currents
Cholinergic Agents
Inhibitory Concentration 50
Neurons
Metal ions
Mucous Membrane
Epithelium
Metals
Chemical activation
Fluids
Electric potential

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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L-type Ca2+ channels in the enteric nervous system mediate oscillatory Cl- secretion in guinea pig colon. / Nishikitani, Mariko; Yasuoka, Yukiko; Kawada, Hideaki; Kawahara, Katsumasa.

In: Tohoku Journal of Experimental Medicine, Vol. 211, No. 2, 08.02.2007, p. 151-160.

Research output: Contribution to journalArticle

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