Mobilization of intracellular Ca(2+) by thromboxane A(2) does not affect Ca(2+)-activated K(+) channels in rat colonic crypt cells.
The effects of 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2)), a stable thromboxane A(2) analogue, and carbachol on colonic Ca(2+)-activated K(+) channels were studied. In indo-1-loaded single cells in isolated rat colonic crypts, both STA(2) (0.1 microM) and carbachol (10 microM) transiently increased intracellular free Ca(2+) concentration ([Ca(2+)](i)) by 136 and 155 nm, respectively. In whole-cell current-clamp experiments of the colonic crypt cells with Cl(-)-free solutions, carbachol (10 microM) hyperpolarized the cell by 19.7 mV, while STA(2) (0.1 microM) did not affect the membrane potential. In the isolated colonic mucosa that was permeabilized mucosally by a monovalent ionophore nystatin in the presence of a serosally directed K(+) gradient, carbachol (10 microM) transiently elicited K(+) current, but STA(2) (0.1 microM) did not. These results indicate that STA(2) elevates [Ca(2+)](i) in rat colonic crypt cells but does not activate basolateral Ca(2+)-activated K(+) channels.
Suzuki
T
T
Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, 930-0194, Japan.
Sakai
H
H
Ikari
A
A
Takeguchi
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009761:Nystatin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018679:Cholinergic Agonists; D007476:Ionophores; D015221:Potassium Channels; D009761:Nystatin; D013928:Thromboxane A2; C037866:STA 2; D002217:Carbachol; D002118:Calcium