| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA; Department of Pharmacology, Yale University, New Haven, CT, USA
2 Department of Pharmacology, Yale University, New Haven, CT, USA
3 Department of Internal Medicine, Yale University, New Haven, CT, USA
4 Aab Institute for Biomedical Research, Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA
5 Department of Pharmacology, Yale University, New Haven, CT, USA; Department of Internal Medicine, Yale University, New Haven, CT, USA
* To whom correspondence should be addressed. E-mail: vazraj{at}hotmail.com.
Colonic K+ secretion stimulated by cholinergic agents requires activation of muscarinic receptors and the release of intracellular Ca2+. However, the precise mechanisms by which this rise in Ca2+ leads to K+ efflux across the apical membrane are poorly understood. In the present study, Northern blot analysis of rat proximal colon revealed the presence of transcripts encoding rSK2 (SK), rSK4 (IK) and rSlo (BK) Ca2+-activated K+ channels. In dietary K+-depleted animals, only rSK4 mRNA was reduced in the colon. Based on this observation, a cDNA encoding the K+ channel rSK4 was cloned from a rat colonic cDNA library. Transfection of this cDNA into CHO cells led to the expression of Ca2+-activated K+ channels that were blocked by the IK channel inhibitor clotrimazole (CLT). Confocal immunofluorescence confirmed the presence of IK channels in proximal colonic crypts and western blotting demonstrated that IK protein sorted to both the apical and basolateral surfaces of colonic epithelia. In addition, transcellular active K+ secretion was studied on epithelial strips of rat proximal colon using unidirectional 86Rb+ fluxes. The addition of thapsigargin or carbachol to the serosal surface enhanced net 86Rb+ secretion. The mucosal addition of CLT completely inhibited carbachol-induced net 86Rb+ secretion. In contrast, only partial inhibition was observed with the BK and SK channel inhibitors, iberiotoxin and apamin, respectively. Finally, in parallel with the reduction in SK4 message observed in animals deprived of dietary K+, carbachol-induced 86Rb+ secretion was abolished in dietary K+ depleted animals. These results suggest that the rSK4 channel mediates K+ secretion induced by muscarinic agonists in the rat proximal colon and that transcription of the rSK4 channel is down-regulated to prevent K+ loss during dietary K+ depletion.
This article has been cited by other articles:
|
|
 |
|
  M. V. Sorensen, J. E. Matos, M. Sausbier, U. Sausbier, P. Ruth, H. A. Praetorius, and J. Leipziger Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion J. Physiol., September 1, 2008; 586(17): 4251 - 4264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ledoux, A. D. Bonev, and M. T. Nelson Ca2+-activated K+ Channels in Murine Endothelial Cells: Block by Intracellular Calcium and Magnesium J. Gen. Physiol., January 28, 2008; 131(2): 125 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Flores, J. E. Melvin, C. D. Figueroa, and F. V. Sepulveda Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4 J. Physiol., September 1, 2007; 583(2): 705 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dong, A. Smith, M. Hovaida, and J. Y. Chow Role of Ca2+-activated K+ channels in duodenal mucosal ion transport and bicarbonate secretion Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1120 - G1128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sausbier, J. E. Matos, U. Sausbier, G. Beranek, C. Arntz, W. Neuhuber, P. Ruth, and J. Leipziger Distal Colonic K+ Secretion Occurs via BK Channels J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1275 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Liao, L. Wang, S. T. Halm, L. Lu, R. E. W. Fyffe, and D. R. Halm K+ channel KVLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl- secretion Am J Physiol Cell Physiol, September 1, 2005; 289(3): C564 - C575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Hoque, V. M. Rajendran, and H. J. Binder Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G956 - G963. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
