Published online before print September 13, 2007, doi: 10.1161/CIRCRESAHA.107.154377
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 American Heart Association, Inc.
Cellular Biology |
Acid-Sensing Ion Channels Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells
From the Cardiovascular Center and Departments of Internal Medicine (Z.-Y.T., Y.L., C.A.W., C.J.B., M.W.C., F.M.A.) and Molecular Physiology and Biophysics (M.W.C., F.M.A.), University of Iowa, Iowa City; and Veterans Affairs Medical Center (M.W.C.), Iowa City, Ia.
Correspondence to Francois M. Abboud, MD, Department of Internal Medicine, University of Iowa, 200 Hawkins Dr, 616 MRC, Iowa City, IA 52242. E-mail francois-abboud{at}uiowa.edu
Carotid body chemoreceptors sense hypoxemia, hypercapnia, and acidosis and play an important role in cardiorespiratory regulation. The molecular mechanism of pH sensing by chemoreceptors is not clear, although it has been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K+ current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using the whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward current in glomus cells that was inhibited by the acid-sensing ion channel (ASIC) blocker amiloride, absent in Na+-free bathing solution, and enhanced by either Ca2+-free buffer or addition of lactate. In addition, ASIC1 and ASIC3 were shown to be expressed in rat carotid body by quantitative PCR and immunohistochemistry. In the current-clamp mode, extracellular acidosis evoked both a transient and sustained depolarizations. The initial transient component of depolarization was blocked by amiloride, whereas the sustained component was eliminated by removal of K+ from the pipette solution and partially blocked by the TASK (tandem-p-domain, acid-sensitive K+ channel) blockers anandamide and quinidine. The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels.
Key Words: carotid body • ASIC • glomus cell • chemoreceptors • pH sensitivity
Related Article:
Circ. Res. 2007 101: 965-967.
This article has been cited by other articles:
 |
|
 |
|
  E. E. Benarroch The arterial baroreflex: Functional organization and involvement in neurologic disease Neurology, November 18, 2008; 71(21): 1733 - 1738. [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Y. Tan, Y. Lu, C. A Whiteis, M. W Chapleau, and F. M Abboud Abstract 1627: Molecular Substrates of Carotid Body Chemoreceptor Activation Circulation, October 28, 2008; 118(18_MeetingAbstracts): S_360 - S_360.
|
|
|
|
 |
|
 S. Trapp, M. Isabel Aller, W. Wisden, and A. V. Gourine A Role for TASK-1 (KCNK3) Channels in the Chemosensory Control of Breathing J. Neurosci., August 27, 2008; 28(35): 8844 - 8850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Drummond, N. L. Jernigan, and S. C. Grifoni Sensing Tension: Epithelial Sodium Channel/Acid-Sensing Ion Channel Proteins in Cardiovascular Homeostasis Hypertension, May 1, 2008; 51(5): 1265 - 1271. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Lopez-Lopez and M. T. Perez-Garcia An ASIC Channel for Acid Chemotransduction Circ. Res., November 9, 2007; 101(10): 965 - 967. [Full Text] [PDF]
|
|