L-type Ca2+ channels in the enteric nervous system mediate oscillatory Cl- secretion in guinea pig colon.
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 neuroepithelial junction. We investigated the inhibitory effects of organic and inorganic Ca2+ channel antagonists on the short circuit current (I(sc)) of colonic epithelia (mucosa-submucosa sheets) mounted in Ussing chambers. The amplitude (412 +/- 37 microA cm(-2)) and frequency (2.6 +/- 0.1 cycles min(-1)) of the Ba2+-induced I(sc) 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 I(sc) 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 microM 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 I(sc) was unchanged over the range of concentrations of the Ca2+ channel antagonists used. Our results show that the oscillatory I(sc) 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.
Nishikitani
Mariko
M
Department of Physiology, Kitasato University School of Medicine, Sagamihara, Japan.
Yasuoka
Yukiko
Y
Kawada
Hideaki
H
Kawahara
Katsumasa
K
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D004594:Electrophysiology; D017615:Enteric Nervous System / Q000502:physiology*; D006168:Guinea Pigs; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D016014:Linear Models; D009474:Neurons / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002413:Cations, Divalent; D002712:Chlorides; D001464:Barium; D014700:Verapamil